Rodents

Infection of Different Strains of Mice with Lawsonia intracellularis Derived from Rabbit or Porcine Proliferative Enteropathy – Lesions in mice included epithelial hyperplasia with inflammation in the ileum and cecum.  Lawsonia antigen was found in early lesions more than late lesions.  Mice reacted differently to Rabbit derived Lawsonia than to Porcine derived Lawsonia which suggests a difference between the two strains.

Immunohistochemical Characterization of Cellular Proliferation in Small Intestinal Hyperplasia of Rats with Hepatic Strobilocercus fasciolaris Infection — Rodents infected with the larvae of Taenia taeniaeformis harbour the intermediate metacestode stage of the parasite, Strobilocercus fasciolaris, within the liver. Infected animals also develop gastric mucosal hyperplasia and  intestinal hyperplasia.

Gastric Lesions and Immune Responses caused by Long-term Infection with Helicobacter heilmannii in C57BL/6 Mice. J. Comp. Path. 2008, Vol. 139, 208e217. Gross lesions include gastric nodules and increased mucosal thickness of the stomach due to gastric epithelial proliferation. Infection also induced the formation of lymphoid follicles in the corpus mucosa and submucosa. Lymphocytes produced IFN-γ (a Th1 cytokine) and IL-10 (a Th2 cytokine), suggesting that both Th1 and Th2 responses are associated.

Human Leptospira interrogans serogroup icterohaemorrhagiae infection (Weil’s disease) acquired from pet rats

Comparative Pathological Study of the Murine Brain after Experimental Infection with Classical Rabies Virus and European Bat Lyssaviruses J. Comp. Path. 2009, Vol. 140, 113e126

European bat lyssaviruses (EBLVs) types 1 (EBLV-1) and 2 (EBLV-2) cause rabies in terrestrial species. Swiss OF-1 mice were inoculated peripherally with strain RV61 (classical rabies virus), RV1423 (EBLV-1) or RV1332 (EBLV-2). The lesions produced, which included perivascular cuffs and gliosis, were more severe after RV1423 or RV1332 infection than after RV61 infection.

Morphological and Immunohistochemical Studies of Spontaneous Mammary Tumours in Siberian Hamsters (Phodopus sungorus)

J. Comp. Path. 2009, Vol. 140, 127e131. Mammary tumours from 12 domestic Siberian hamsters. Histopathology revealed three subtypes: simple adenoma, tubulopapillary carcinoma, and complex carcinoma. In five cases of malignant mammary tumour, focal infiltration into the surrounding fibrous connective tissue was present; however, no invasion of either lymphatics or blood vessels was observed. Ten of the 12 tumours were positive for androgen receptor and all were negative for progesterone receptor. Five tumours expressed oestrogen receptor alpha.

Spontaneous Exocrine Pancreas Hypoplasia in Specific Pathogen-free C3HeB/FeJ and 101/H Mouse Pups Causes Steatorrhea and Runting. Vol 57, No 2 April 2007 This condition resembles exocrine pancreas hypoplasia, but the inheritance is complex. A wider implication is that runting coupled with steatorrhea are phenotypic criteria to suspect pancreatic disease that could be used in the context of a mouse N-ethyl-N-nitrosourea-mutagenesis program to identify potential mutants with defects in pancreas development.

Effects of Leukotriene Inhibition on Pulmonary Morphology in Rat Pup Lungs Exposed to Hyperoxia. Vol 57, No 2 April 2007.  Pulmonary changes including edema, hemorrhage, alveolar macrophage influx, and Type II pneumocyte proliferation.

Pancreaticoduodenal Arterial Rupture and Hemoabdomen in ACI/SegHsd Rats with Polyarteritis Nodosa. Vol 57, No 4 August 2007.  Although arterial rupture is a known complication of polyarteritis nodosa in humans, this case series is the first to document arterial rupture and hemoabdomen in rats with PAN.

An Experimental Model of Actinobacillus suis Infection in Mice. Vol 57, No 4 August 2007. These experiments demonstrate that mice can be infected with A. suis and subsequently develop pneumonia and bacteremia comparable to that seen in pigs, suggesting that mice may be used as a model for studying infection in swine.

Phenotypic Characterization of Spontaneously Mutated Rats Showing Lethal Dwarfism and Epilepsy.  Vol 57, No 4 August 2007.  Histologically, increased apoptotic germ cells, lack of spermatocytes, and immature Leydig cells were found in the mutant testes, and extracellular vacuoles of various sizes were present in the hippocampus and amygdala of the mutant brain. Mutant rats had significantly increased concentrations of plasma urea nitrogen, creatinine, and inorganic phosphate, as well as decreased concentrations of plasma growth hormone. Hereditary analysis showed that the defects were inherited as a single recessive trait. We have named the hypothetically mutated gene as lde (lethal dwarfism with epilepsy).

Natural Dental Caries in Molars of Osteogenic Disorder Shionogi Rats. Vol 57, No 6 Pages 590–593. defective in ascorbic acid biosynthesis. dysfunctional bone formation and display various dental abnormalities.

Gender Influences Infectivity in C57BL/6 Mice Exposed to Mouse Minute Virus. Vol 57, No 1

February 2007.  MMV = Parvovirus.

Murine Gammaherpesvirus 68: A Model for the Study of  Epstein-Barr Virus Infections and Related Diseases. Vol 57, No 1

February 2007.  EBV is associated with the development of B-cell lymphoproliferative disorders, several malignant cancers, the syndrome of infectious mononucleosis, and chronic interstitial lung disease.

Pathobiology and Management of Laboratory Rodents Administered CDC Category A Agents. Vol 57, No 1 February 2007.  Category A infectious agents include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague), variola major virus (smallpox), Francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers.

Abetalipoproteinemia Induced by Overexpression of ORP150 in Mice. Vol 57, No 3 June 2007.  ORP150 is an endoplasmic-resident, hypoxic stress-induced protein.  overexpression of ORP150 in mice leads to abetalipoproteinemia with alteration of glucose and lipid metabolism. growth retardation concomitant with vacuolar degeneration in the heart.

High-carbohydrate Diets Affect the Size and Composition of Plasma Lipoproteins in Hamsters (Mesocricetus auratus). Vol 58, No 2 April 2008. High-carbohydrate diets reduce plasma low-density lipoprotein (LDL)–cholesterol but also provoke the appearance of an atherogenic lipoprotein profile (ALP). Characterized by high plasma triglyceride, small dense LDL, and reduced high-density lipoprotein ((HDL) cholesterol, an ALP is associated with insulin resistance.

Utility of AntiPax5 in the Diagnosis of Lymphoproliferative Disorders and Neoplasia in Mice. Vol 58, No 3 June 2008. Pax5 expression (detected by immunohistochemistry using antiPax5) offers greater specificity and sensitivity because of its earlier expression during B-cell differentiation, its ability to detect all committed B cells, and its restriction to the B-cell lineage.  Better than CD45R/B220 antigen (B220) (this is sometimes on CD8+ and NK T cells). NK cells are CD56+ and CD8 variable.

Histopathologic Findings and Establishment of Novel Tumor Lines from Spontaneous Tumors in FVB/N Mice. Vol 58, No 3 June 2008. All tumors in male mice were lung alveolar–bronchiolar (AB) neoplasms, except for 1 testis interstitial cell tumor. In female mice, histopathologic examination revealed 48 lung AB tumors, 27 mammary gland tumors, 13 ovarian tumors, and 14 other tumors. Several of these spontaneous tumors have been transplanted into FVB/N mice. One mammary adenocarcinoma (MCaP0008) and 1 lung AB carcinoma (LAP0297) were successfully transplanted subcutaneously and passaged serially in vivo.

Spontaneous Vulvar Papillomas in a Colony of Mice Used for Pancreatic Cancer Research. Vol 58, No 3 June 2008. interaction between the genetic background of the mice and the introduced Kras oncogene may be responsible for these papillomas.

An outbreak of acute aflatoxicosis on a chinchilla (Chinchilla lanigera) farm in Argentina.  J Vet Diagn Invest 20:853–856 (2008). Chinchillas (Chinchilla lanigera) are known to be very sensitive to aflatoxins- Aflatoxins B1, B2, G1, and G2 were in the feed- but was positive for aflatoxin B1 in quantities that exceeded the recommended levels.  Macroscopic inspection of livers revealed general enlargement, pale yellowish coloration, hypertrophy, rounded borders, and increased friability. Size and color were remarkably different from a healthy organ. Histopathologic analyses of hepatic parenchyma showed severe, diffuse cytoplasmic vacuolation of hepatocytes. Sudan III staining confirmed the presence of lipid within the vacuoles.

Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of Anaplasma phagocytophilum.  Vet Pathol 44:64–73 (2007). Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum. Gross- Splenomegaly.  Microscopic – inflammatory lesions in the lung and liver, hyperplastic lesions on the spleen.

Characterization of a Rat Subcutaneous Malignant Fibrous Histiocytoma and Its Tumor Lines, with Reference to Histiocytic Features.  Vet Pathol 44:151–160 (2007). Fusiform cells arranged in interlacing bundles with fibrous stroma. Occasional giant cells with bizarre nuclei were observed. positive reaction to vimentin and lysosomal enzyme markers such as acid phosphatase (ACP) and nonspecific esterase (Non-SE).

Hermaphroditism in 3 Chimeric Mice. Vet Pathol 44:249–252 (2007).  Histologically, mice Nos. 1 and 3 were true hermaphrodites with unilateral ovotestes, while mouse No. 2 was a pseudohermaphrodite with ovarian tissue only.

Atrioventricular Valvular Angiectasis in Sprague-Dawley Rats.  Vet Pathol 44:407–410 (2007). The angiectasis was observed predominately on the septal cusp of the right AV valve and located near the AV ostium in 57 of 62 animals. The angiectases were single or multiple, ranging from 40 to 300 mm in diameter and were characterized by light microscopy as bloodfilled dilatations lined by  endothelium..

Hermaphroditism in a Sprague-Dawley Rat.  Vet Pathol 44:418–420 (2007). A spontaneous case of unilateral true hermaphroditism was observed during the routine necropsy of a 9-week-old presumed female Sprague-Dawley rat on a repeat-dose toxicity study. There were no drug-related effects observed. True hermaphroditism is rare in rats, and despite the large numbers of rats examined annually, few cases are reported in the literature.

Auricular Chondritis Caused by Metal Ear Tagging in C57BL/6 Mice. Vet Pathol 44:458–466 (2007).  Histopathologically, there were observed severe chondritis with extensive granulomatous inflammation, newly formed cartilage nodules, and osseous metaplasia accompanied by cellular infiltrates, such as CD4 T lymphocyte, macrophages, neutrophils, and mast cells, and expression of Th1 cytokines, such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 in the tagged ear. Based on these results, we concluded that the release of copper and iron ions from the metal ear tags played a major role in the onset of auricular chondritis. Subsequent cellular interactions, such as CD4 T cells, macrophages, fibroblasts, and mast cells, mediated by cytokines, such as tumor necrosis factoralpha and interferon-gamma, caused an autoimmune response that may have led to the progression of auricular chondritis as an autoimmune disease.

Eosinophilic Substance is ‘‘Not Amyloid’’ in the Mouse Nasal Septum. Vet Pathol 44:796–802 (2007).  An eosinophilic substance (ES) is usually observed in the mouse nasal septum and increases in volume with aging. It has been described as amyloid in textbooks and one report. However, it has been described as ‘‘not amyloid’’ in other reports because there was a negative reaction to Congo red. The ES reacted negatively to Congo red but was strongly positive to periodic acid–Schiff reaction with prior diastase treatment. In the electron microscope observation, the ES consisted of amorphous material and collagen, but no nonbranching fibrils.  The above-mentioned findings indicated that the ES was not amyloid and suggested the ES might consist of not only collagen but also complex carbohydrate, which was produced by the nasal gland epithelial cells.

Comparative Pathological Study of the Murine Brain after Experimental Infection with Classical Rabies Virus and European Bat Lyssaviruses: European bat lyssaviruses types 1 (EBLV-1) and 2 (EBLV-2) cause rabies in terrestrial species. Swiss OF-1 mice were inoculated peripherally with strain RV61 (classical rabies virus), RV1423 (EBLV-1) or RV1332 (EBLV-2). In virus the lesions non-suppurative  meningoencephalitis, neuronophagia, focal gliosis and lymphocytic perivascular infiltration. The lesions were more severe European lyssa then classic lyssavirus.  T cells were the predominant lymphocytic component.

Morphological and Immunohistochemical Studies of Spontaneous Mammary  Tumours in Siberian Hamsters: Mammary tumours from 12 domestic Siberian hamsters (11 females, 1 male) were examined. Histopathology revealed three subtypes: simple adenoma, tubulopapillary carcinoma, and complex carcinoma. Ten of the 12 tumours were positive for androgen receptor.

Ocular Albinism and Hypopigmentation Defects in Slc24a5–/– Mice Vet Path 2008 Mar: mice with a targeted mutation in Slc24a5, a gene encoding a putative cation exchanger were constructed. Mice were viable, fertile, and indistinguishable by coat color from their heterozygous and wild-type litter mates. Ophthalmoscopic examination revealed diffuse retinal hypopigmentation, and a histologic examination of the eye confirmed the presence of moderate-to-marked hypopigmentation of the retinal pigmented epithelium (RPE), ciliary body, and iris pigment epithelium (IPE). Hypopigmentation was most severe in the anterior layer cells of the IPE, where melanosomes were smaller, paler. Milder reductions in melanosome size and pigmentation were noted in neural crest–derived melanocytes

A Novel Immunohistochemical Marker of Normal and Neoplastic Melanocytes in Formalin-fixed, Paraffin-embedded Tissues of Albino Rats Vet Path 2008 May:  In conclusion, PNL2 is direct against a fixative- and  decalcific-resistant  melanocyte-associated  antigen,  and  has  high  specificity  against  normal  and neoplastic melanocytes of albino rats.  In amelanotic melanoma, the tumor  cells  consisted  of  spindle  cells  with  eosinophilic  cytoplasm  without  melanin  granules. PNL2 consistently stained cytoplasm in all amelanotic melanoma cells. In contrast, the nonmelanocytic tumor cells were not labeled.

Harderian Gland Neoplasms in Captive, Wild-caught Beechey Ground Squirrels (Spermophilus beecheyi ) Vet Path 2008 May: The Harderian gland is a bilobed, tubuloalveolar accessory lacrimal gland, found in many vertebrate groups  such  as  amphibians,  reptiles,  birds,  and mammals, including various species of laboratory rodents. The gland is located within the medial part of the orbit, and it secretes onto the surface of the nictitating membrane. The mammalian Harderian gland  secretion  is  primarily  composed of  lipids; however,   in   rodents,   the   gland   also   produces porphyrins and inoleamines.  The   Beechey   ground   squirrel   (Spermophilus beecheyi)  has  been  studied  as  a  model  of  human hepatitis  B  virus  (HBV)  infection  because  of  the occurrence  of  a  natural  infection  with ground squirrel hepatitis virus (GSHV), a member of the hepadnavirus family  along with  HBV  and wood- chuck hepatitis virus

Skin Morphology of Thyroidectomized Rats. Vet Pathol 45:505–511 (2008). Histologically, all of the rats in the TD group exhibited epidermal thinning from 12 weeks after surgery. Many hair follicles were  in  the telogen phase:  the  bulbs  and  papillae  were  involuted  and  had  migrated  towards  the epidermis. Hair follicle atrophy involving thinning of the outer root sheath and the inner root sheath was often observed. The immunoreactivities of antithyroid hormone receptors a and b in the outer root sheaths of 5 of the TD rats were weaker than those of control rats.

Review Paper: Preclinical Models of Psoriasis.  Vet Pathol 45:563–575 (2008). focal to coalescing raised cutaneous plaques with consistent scaling and variable erythema.  the underlying mechanisms involve a complex interplay between epidermal keratinocytes, T lymphocytes as well as other leukocytes (including dendritic cells and other antigen presenting cells [APCs]), and vascular endothelium..

Histopathologic and Immunohistochemical Characterization of Nipah Virus Infection in the Guinea Pig.  Vet Pathol 45:576–585 (2008). Humans infected with NiV show a widespread multisystemic vasculitis with most severe clinical and pathologic manifestations in the brain, lungs, and spleen.  A unifying feature of the damage for all affected tissues was necrosis and macrophagic inflammation of the vasculature, chiefly in arterioles, capillaries, and venules. Inoculation of guinea pigs intraperitoneally with NiV produces a disease with considerable resemblance to the disease in humans, but with reduced pulmonary involvement and marked infection of urinary bladder and the female reproductive tract.

Pancreatic Metaplasia in the Gastro-achlorhydria in WTC-dfk Rat, a Potassium Channel Kcnq1 Mutant.  Vet Pathol 45:586–591 (2008). The WTC–deafness Kyoto (dfk) rat is a new mutant characterized by deafness and abnormal, imbalanced behavior.  The most characteristic pathologic feature in the stomach was the appearance of hypertrophic gastric glands in the stomach body. The hypertrophic cells had many eosinophilic granules in their cytoplasm, and these granules were stained red with Azan stain; stained positively for trypsinogen, amylase, and chymotrypsin; and did not stain positively for pepsinogen when using immunohistochemical analysis. These staining results suggested a metaplasia toward a pancreatic acinar cells.  The parietal cells in WTC-dfk rats were negative for KCNQ1 immunohistochemical analysis. These findings indicate that a deficiency in rat Kcnq1 provokes an abnormal proliferation and differentiation of gastric glandular cells. KCNQ1 plays an important role in K+ homeostasis.

Spontaneous Tumors in Domestic Hamsters.  Vet Pathol 45:674–680 (2008).  In the Djungarian hamsters, almost all tumors were integumental, whereas hematopoietic tumors were the most common type in the Syrian hamsters. The most common integumental tumors in the Djungarian hamsters were mammary tumors, atypical fibromas and papillomas.  In the Syrian hamsters, plasmacytomas and lymphomas were the most common tumors.

Malignant Amelanotic Melanoma Behind the Left Eye in a Female Crj:CD(SD)IGS Rat: A Case Report.  Vet Pathol 45:681–684 (2008). spindle-shaped, epithelioid, anaplastic melanoma cells, and had prominent eosinophilic cytoplasm and nuclei with a greater variation in size. Immunohistochemically, almost all of the tumor cells were positive for antimelanoma, PNL2 antibody. Ultrastructurally, the tumor cells were rich in small vesicles containing fine granules and filamentous structures. This is the first report describing an amelanotic melanoma in the head of an albino rat

REVIEW Paper: Pathophysiology of Myocardial Reperfusion Injury: The Role of Genetically Engineered Mouse Models.  Vet Pathol 45:698–706 (2008). MI-R injury is characterized by the formation of oxygen radicals upon reintroduction of molecular oxygen to the ischemic tissue, resulting in widespread lipid and protein oxidative modifications, mitochondrial injury, and cell death. In addition, studies have shown that MI-R is characterized by an inappropriate immune response in the microcirculation, resulting in leukocyteendothelial cell interactions mediated by the upregulation of both leukocyte and endothelial cell adhesion molecules. Furthermore, MI-R ameliorates the production of certain cardioprotective factors such as nitric oxide.

Plasticity of Cloned Canine Mammary Spindle Cell Tumor, Osteosarcoma and Carcinoma Cells.  Vet Pathol 45:803–815 (2008). Our results point to plasticity in canine mammary tumors, as shown both by morphologic criteria and by expression patterns for lineage specific markers

A Pregnant Mouse Model for Bovine Tritrichomonas foetus Infection.  Vet Pathol 45:849–864 (2008). Lesions in pregnant and nonpregnant infected mice, including suppurative and eosinophilic vaginitis; cervicitis; endometritis with distension of the uterine lumen; endometrial ulceration; and glandular ectasia, with neutrophils in the glandular lumen and loss of gland epithelium, were similar to those in cattle. The decidua and placenta were multifocally necrotic. Immunohistochemistry demonstrated trichomonads in vaginal folds and uterine glands, and adjacent to fetal tissues.

Unexpected Preferential Brain Metastases with a Human Breast Tumor Cell Line MDA-MB-231 in BALB/c Nude Mice.  Vet Pathol 45:941–944 (2008).  We report a study in which injection of MDA-MB-231 cell line led to brain rather than bone metastasis. Unexpected alterations in biological behavior are an important confounding variable in the use of tumor cell lines, and the occurrence and cause of such variants is poorly documented.

REVIEW PAPER: A Review of the Pathology of Abnormal Placentae of Somatic Cell Nuclear Transfer Clone Pregnancies in Cattle, Sheep, and Mice. Vet Pathol 45:865–880 (2008). the probability of a successful and complete pregnancy is less than 5%. Failures  of  SCNT  pregnancy  are  associated  with  placental  abnormalities,  such  as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium, and altered basement membrane. evidence  implicates  aberrant reprogramming of donor nuclei by the recipient oocyte cytoplast, resulting in epigenetic modifications of key regulatory genes essential for normal placental development

Spontaneous cutaneous mast cell tumor with lymph node metastasis in a Richardson’s ground squirrel (Spermophilus richardsonii ).  J Vet Diagn Invest 21:156–159 (2009). Histologically, the nodules were composed of a proliferation of spindloid to pleomorphic cells that sometimes formed sheets and fascicular to storiform patterns. Diffuse infiltration of eosinophils was also noted. The results of immunohistochemistry indicated positive labeling for vimentin, mast cell tryptase, c-kit, and Ki-67. Toluidine blue stain revealed fine, metachromatic, cytoplasmic granules. The histologic diagnosis was mast cell tumor.

Alcian Blue and Pyronine Y Histochemical Stains Permit Assessment of Multiple Parameters in Pulmonary Disease Models: Mucus expression, elastic fiber integrity, and mast cell numbers are important morphologic parameters that are used to gauge chronic pulmonary disease progression and severity. With above mentioned stain, acidic mucins were deep blue (sialylated mucins), red (sulfated mucins), or variably purple (mixture of sialylated/sulfated mucins), Elastic fibers stained red; Mast cells had red to red-purple granular cytoplasmic staining.

Effects of 4-n-Octylphenol (OP) on the Induction of Mammary Tumors Induced by 7,12-Dimethylbenz[a]anthracene in Rats: administration of a large dose of a weak estrogenic endocrine disruptor, such as OP, for a long period does not affect female mammary carcinogenesis nor male mammary tumor incidence though a weak influence on male mammary tumor growth may have occured.

The Role of Inflammation in Mouse Pulmonary Neoplasia: Inflammation is risk factor for development of cancer. The most common inflammatory cell type in tumor tissue is macrophage. Tumor tissue is sensitive to growth inhibitory properties of glucocorticoids. PGE2 has pro-tumorigenic and PGI2 has anti-tumorigenic properties, deficiency of TNF, TNFr, IL-10 reduces carcinogenesis, TLR-4 is protective in carcinogenesis, TLR-4 deficient mice are more susceptible to tumor. iNOS deficient mice has less chances of lung cancer.

Ectonucleoside Triphosphate Diphosphohydrolase Type 5 (Entpd5)–Deficient Mice Develop Progressive Hepatopathy, Hepatocellular Tumors, and Spermatogenic Arrest: Ectonucleoside triphosphate diphosphohydrolase type 5 is a soluble enzyme that hydrolyzes purine nucleoside diphosphates. Genetic inactivation of ENTPD5 in mice resulted in hepatopathy (centrilobular heptocyte hypertrophy) and aspermia.

Hydronephrosis and Urine Retention in Estrogen-Implanted Athymic Nude Mice: Subcutaneous estrogen pellet implantation is commonly practiced to induce tumor promotion in nude mice for xenograft tumor modeling. In this study s/c implantation of estrogen resulted in dilated urinary bladder and hydronephrosis.

Neonatal Death in Mice Lacking Cardiotrophin-like Cytokine is Associated with Multifocal Neuronal Hypoplasia Vet Pathol 46:514–519 (2009). Mice with null mutations of ciliary neurotrophic factor (Cntf) receptor alpha (Cntf-Ra), or cytokine-like factor 1 (Clf), one component of Cntf-II (a heterodimeric Cntf-Ra ligand), die as neonates from motor neuron loss affecting the facial nucleus and ventral horn of the lumbar spinal cord.  Exposure  to  cardiotrophin-like  cytokine  (Clc),  the  other  putative  Cntf-II  element,  supports motor neuron survival in vitro and in ovo.

Progressive proliferative & dysplastic typhlocolitis in aging Syrian hamsters naturally infected with Helicobacter spp.: a spontaneous model of inflammatory bowel disease. pp2-14. Jan 2006  AR. Hamsters and Helicobacter spp. infection: large bowel hyperplasia, and dysplasia in ileocecocolic junction/ Tumors: malignant fibrous histiocytoma & round cell sarcoma./ Hamsters and enteric disease: Clostridium difficile overgrowth: typically causes necrotizing fatal typhlocolitis; linked to proliferative typhlocolitis in adults/ Lawsonia intracellularis: proliferative enteritis /  Giardia: enterotyphlocolitis in aging hamsters/ Campylobacter jejuni: reservoirs Round cell tumor such as gastric lymphomas have been associated with: H. pylori in humans, H. mustelae in ferrets, H. felis in mice.

Gonadectomy-induced adrenocortical neoplasia in the domestic ferret & laboratory mouse. pp97-117. March 2006  AR [see AR’s comprehensive summary for further details]

Sex steroid-producing adrenocortical adenomas and carcinomas occur frequently in neutered ferrets

Prepubertal gonadectomy elicits similar tumors in certain inbred/genetically engineered strains of mice

Mice & ferrets: neoplastic adrenocortical cells functionally resemble gonadal steroidogenic cells and arise from progenitors in the subcapsular or juxtamedullary region

Chronic ­ in LH that follows ovariectomy/orchiectomy is a prerequisite for neoplastic transformation

Gonadectomy alters the plasma/local concentrations of steroid hormones and other factors that affect adrenocortical tumor development including inhibins, activins, and Mullerian inhibiting substance

GATA-4 immunoreactivity is a hallmark of neoplastic transformation

Synergistic interactions among GATA-4, steroidogenic factor-1 (SF-1), & other transcription factors enhance expression of inhibin-a & genes critical for sex steroid production such as CYP450 17a-hydroxylase/17,20 lysase & aromatase

Gonadectomy-induced adrenocortical neoplasia observed in ferrets, mice, rats, guinea pigs, & hamsters

Adrenocortical carcinomas are associated with prepubertal gonadectomy of CE mice

The comparative pathology of Clostridium dificile-associated disease. REVIEW. pp225-40. May 2006  AR

C. difficile: Most species® cecum & colon; Foals & rabbits® jejunum

Most common in Syrian hamsters, horses, neonatal pigs; Sporadic in other species

Virulence factors (exotoxins): toxin A (TcdA) and toxin B (TcdB)

Receptor-mediated endocytosis of toxins (Cell surface receptor identified for TcdA, but not TcdB)® endosomal acidification® conversion of toxin to active form in cytosol® disrupt Rho-subtype intracellular signaling molecules® disrupt actin cytoskeleton® catastrophic for cellular function (inflammation & neurogenic stimuli also involved)

Laboratory Animal

Expression of terminal differentiation proteins defines stages of mouse mammary gland development. pp36-49. Jan 2006  MT  [tough article]

–  IHC on paraffin sections used to evaluate ptn expression while preserving architecture; assessed changes in patterns of expression of terminal differentiation markers throughout development of mouse mamm. gland

–  Expression of SMA & keratin 5 (K5), K8/18, K14 influenced by development stage of mamm. gland

K5 & SMA restricted to basal cells; K14 consistently expressed by basal cells, & in scattered luminal cells from post-conception day (PCD) 13.5 thru puberty

–  K8/18 of luminal cells heterogenous at all times (suggests this layer has cells w/variety of biological fxns)

K6 not expressed at any stage – so this intermediate filament NOT a marker of mamm. gland stem cell (K6 typically associated w/epidermal proliferation, & is seen in some preneoplastic & neoplastic mouse mamm. lesions)

No expression of K1, K10, K13, K15, filaggrin, involucrin, or loricrin at any stage (last 3 are epidermal differentiation markers in stratum granulosum of nml epidermis; K1 & K10 are suprabasal terminal differentiation ptns)

Spontaneous Aortitis in Balb/c Mouse:  Background vascular lesions.

Epithelial-Stromal Tumor of the Seminal Vesicles in the Transgenic Adenocarcinoma Mouse Prostate Model: transgenic adenocarcinoma mouse prostate (TRAMP) model, designed for researching human prostatic cancer, was genetically engineered to harbor a transgene composed of the SV-40 Large-T cell and the TRAMP mouse develops tumors in the seminal vesicles. Neoplastic stromal cells that emerged multicentrically just beneath the epithelium, densely packed between the epithelium. Proliferative mesenchymal cells were lined by cuboidal to columnar epithelium. esion in the seminal vesicles is epithelial-stromal tumor.

Gastritis-associated Adenocarcinoma and Intestinal Metaplasia in a Syrian Hamster Naturally Infected with Helicobacter Species: an invasive adenocarcinoma at the pyloric-duodenal junction in one of nine hamsters at a site of helicobacter-associated inflammation and marked intestinal metaplasia. Ceca of 9 /9 animals were culture positive and PCR positive for Helicobacter spp. 8/9 hamsters including the animal with the gastric adenocarcinoma had locally extensive chronic gastritis with intestinal metaplasia. However, argyrophilic bacteria were demonstrated only within the stomach of the hamster with gastric adenocarcinoma. Mongolian gerbils, ferrets, C57BL/6, and INS-GAS mice develop gastric cancer following Helicobacter infection. Only gerbils and hamsters infected with Helicobacter spp. develop intestinal metaplasia similar to humans.

Fatal Placental Subinvolution in a Captive Capybara: An adult, captive-born female capybara died of systemic thrombosis and hemoperitoneum associated with placental subinvolution. Grossly, the uterus was enlarged, segmentally thickened, and associated with a large blood clot. There was hemometra and a large ovoid mass in each uterine horn and the right uterine horn wall had a small perforation over the mass. The mesometrial veins were markedly dilated due to thrombosis and occasionally perforated. Histo: the uterine masses consisted of partly necrotic placental and subplacental tissue. The uterine wall surrounding the masses had full-thickness coagulative necrosis of the myometrium and diffuses endometrial

Extramedullary Plasmacytoma of the Salivary Gland in Two Syrian Hamsters: ulceration with abundant syncytiotrophoblast-like cells within capillaries.

Mycoplasma pulmonis and Lymphoma in Bioassays in Rats.  Vet Pathol 46:952–959 (2009). Because the lymphoma type, cellular morphology, and organ distribution reported in these studies are atypical of lymphoma in rats, because lymphocyte  and  plasma  cell  accumulation  in  the  lung  is  characteristic  of  M.  pulmonis  disease,  and because  M.  pulmonis  disease  can  be  exacerbated  by  experimental  manipulations,  including  chemical treatment, we suggest that a plausible alternative explanation for the reported results of these bioassays is  that  the  studies  were  confounded  by  M.  pulmonis  disease  and  that  lesions  of  the  disease  were interpreted as lymphoma.

Histopathology of Naturally Transmitted ‘‘Rat Respiratory Virus’’: Progression of Lesions and Proposed Diagnostic Criteria.  Vet Pathol 46:992–999 (2009). Irregular gray-white lesions suggestive of interstitial pneumonia were grossly evident.   multifocal, lymphohistiocytic interstitial pneumonia or prominent perivascular lymphoid cuffing from weeks 5 through 13.

Expression of Tumor Invasion Factors Determines Systemic Engraftment and Induction of Humoral Hypercalcemia in a Mouse Model of Adult T-cell Leukemia. Vet Pathol 46:1003–1014 (2009). Infection  with  human  T-cell  leukemia  virus  type  1  (HTLV-1)  leads  sometimes  to  the development of adult T-cell lymphoma/leukemia (ATL).  In mice, inoculation of HTLV-1 cell lines mostly leads to development of localized lymphomas.  Inoculation of MET-1 cells into NOD/SCID mice provided the best model system for slowly developing T-cell leukemia with multiple organ involvement. In leukemic mice, an increase in serum calcium levels correlated with expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand on leukemic cells and secretion of parathyroid hormone–related  protein  and  interleukin-6. In  contrast  to  the  other  cell  lines  that  did  not  spread systemically, MET-1 expressed both the adhesion molecules CD11a (LFA-1a) and CD49d (VLA-4a) and produced or induced expression of matrix metalloproteinases 1, 2, 3, and 9, thus underlining the importance  of these  molecules  in the spread  of adult T-cell  leukemia  cells.

Re-evaluation of Kidney Histopathology from 13-Week Toxicity and Two-Year Carcinogenicity Studies of Melamine in the F344 Rat: Morphologic Evidence of Retrograde Nephropathy. Vet Pathol 46:1248–1257 (2009) DOI: 10.1354/vp.08-VP-0317-F-FL.   tubule dilatation and tubule basophilia, fibrotic scars, in which tubule loss and collagen deposition were prominent, —ascending form of nephropathy. The term retrograde nephropathy is considered to be the appropriate nomenclature for both the acute and chronic lesions. It can be speculated that melamine precipitation in the lower urinary tract created pressure effects through transient obstruction leading to the renal changes. These changes were different from those involved in a major US outbreak of renal disease and death in cats and dogs associated with triazine-contaminated pet food, in which crystalluria from insoluble melamine/cyanuric acid complexes occurred in the kidney. However, the rat findings may be relevant to melamine-associated kidney disease recently reported in infants in China

Diagnostic Exercise: Sudden Death in a Mouse with Experimentally Induced Acute Myeloid Leukemia. Vet Pathol 46:1301–1305 (2009). Histologic analysis confirmed the mouse as being affected by a progressive myeloid leukemia, with infiltration of the spleen, bone marrow, liver, kidneys, and lungs. Variably sized intravascular clumps (emboli) of dense basophilic material admixed with necrotic or lytic neoplastic cells were also observed in multiple organs. A positive reaction to Feulgen and Hoechst stain confirmed the high content in chromatin of these basophilic emboli. Cleaved caspase-3 activity was demonstrated both in the leukemic infiltrates and among the intravascular necrotic or lytic neoplastic cells accompanying the basophilic emboli. A diagnosis of acute tumor lysis syndrome related to therapy-induced massive necrosis and/or apoptosis of leukemic cells with subsequent dissemination of emboli of chromatin was proposed.

A Rhabdomyoma Within a Multilocular Thymic Cyst in a p53-Null Mouse. Veterinary Pathology 47(1) 132-136.  varying-sized cysts lined with simple squamous epithelial cells to columnar ciliated cells. Also present within this mass was a large aggregate of loosely arranged fusiform-shaped cells. These cells also were found in smaller numbers in the connective tissue surrounding the cysts. The larger aggregate of fusiform cells was positive for desmin and S-100 and negative for smooth muscle actin. Electron microscopy revealed well-formed Z lines and I bands of skeletal muscle phenotype.

Spontaneous Basal Cell Carcinoma in a 7-Week-Old Sprague-Dawley Rat. Veterinary Pathology 47(1) 137-139.  well-delineated reddish-brown subcutaneous mass. basaloid cells in lobular and cribriform growth patterns and with a high mitotic rate. Immunohistochemically, cytokeratin 14 (an indicator for basal keratinocytes of the epidermis) showed strong reactions through-out the whole tumor, and cytokeratin 18 showed weak but positive reaction in the majority of nested tumor cells.

Molecular Basis for Hair Loss in Mice Carrying a Novel Nonsense Mutation (Hr

rh-R ) in the Hairless Gene (Hr). Veterinary Pathology 47(1) 167-176. Vibrissae were normal but became sparse with age (Fig. 2). Nail length increased, and older adult mice (about 6 months of age) displayed overgrown nails that curled under the foot pad (onychogryposis). Infundibula were mildly ectatic and filled with laminated cornified cells. The stratum granulosum extended from the epidermis to the entrance of the sebaceous gland duct. The stratum granulosum was mildly hyperplastic (hypergranulosis) with prominent large basophilic keratohyalin granules. As the mutant hair follicle entered catagen, a rim of keratinocytes surrounded the dermal papilla (Fig. 8). At 21 days of age, when hair follicles were in telogen or early anagen, the remaining club hair was still present in many follicles in which the infundibulum  was  ectatic  and  filled  with  laminated cornified material (Fig. 9). No club hairs remained at 5 weeks of age. As follicles entered catagen at 5 weeks of age, a thin serpentine-shaped band of cells, surrounded by a thick hyaline membrane (glassy membrane), extended from the abnormal ectatic infundibulum to the dilated deep dermal cyst, which developed  from  keratinocyte  remnants  that  surrounded  the dermal papilla  Loss of Hr expression led to upregulation of a number of genes involved in epidermal regeneration and differentiation, before the point at which obvious morphological lesions were detected in sections of dorsal skin. early markers of keratinocyte differentiation such as keratins 1 and 10 and Fos. Also in this set are  genes  linked  more  specifically  to  the  hair  follicle, including Mycn, Hoxd13, Efna3, and Bmi. Bmi1 has been implicated as a self-renewal gene expressed in hair follicle stem cells.

Undifferentiated carcinoma of the salivary gland in a chinchilla (Chinchilla lanigera). J Vet Diagn Invest 22:152–155 (2010). multilobulated, cystic, neoplastic mass extended subcutaneously over the ventral and lateral neck with metastatic spread to submandibular lymph nodes, spleen, liver, and lungs. Neoplastic cells were strongly positive for vimentin and pan-cytokeratin but were negative for alpha–smooth muscle actin, S100, and myosin; no intracytoplasmic myofibrils were detected on phosphotungstic acid hematoxylin staining. Histologic and immunohistochemical examination of the mass led to a diagnosis of undifferentiated carcinoma of the salivary gland.


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