Abstract

The kidneys from six immunodeficient mice examined by Cerberus Sciences and the Animal Resources Centre, displayed karyomegaly with pale eosinophilic, intranuclear inclusions upon histopathological examination. Electron microscopy performed on kidney tissue from 5/6 mice demonstrated margination of the chromatin in large nuclei. Laboratory tests were used to detect nucleic acid of papillomaviruses, polyomaviruses, circoviruses and anelloviruses (4/6 mice), a specific PCR was used to detect murine polyomavirus (1/6), and a panel of serological tests was used to detect seroconversion to major murine pathogens (1/6). All molecular and serological tests were negative. Immunohistochemistry using polyclonal anti-bovine papillomavirus type 1 (BPV-1) L1 antibody, Camvir monoclonal anti-papillomavirus antibody (directed against the seven amino acids GFGAMDF found in human papillomavirus (HPV) 16 L1 protein), a commercially available mixture of two monoclonal antibodies, anti-BPV-1 L1/1H8 + Camvir antibodies, and a monoclonal anti-Hsc70 antibody revealed specific, positive staining of murine renal tubular epithelial intranuclear inclusions in 6/6 mice using the anti-BPV-1 L1 containing antibodies only. Methyl pyronin green, PAS and Feulgen histochemical reactions revealed that the intranuclear inclusions did not consist of RNA, DNA or carbohydrate. An immunohistochemical method now exists that can be used to confirm and evaluate suspected cases of murine inclusion body nephropathy.

Highlights

  • Veterinary pathologists examining mouse kidneys have occasionally noted the presence of large, eosinophilic intranuclear inclusions and karyomegaly in the renal tubular epithelium of immunodeficient mice [1]

  • Microbiology, parasitology, necropsy, histopathology, PCR and immunohistochemistry investigations have, to date, all failed to detect a pathogen that might be associated with these murine renal intranuclear inclusion bodies, and the tubular inclusions have so far been considered an idiopathic, degenerative lesion [2]

  • The majority of intranuclear inclusions were noted in tubular epithelium of the renal cortex, occasional inclusions were noted in the tubular epithelium of the collecting ducts of the medulla

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Summary

Introduction

Veterinary pathologists examining mouse kidneys have occasionally noted the presence of large, eosinophilic intranuclear inclusions and karyomegaly in the renal tubular epithelium of immunodeficient mice [1]. Such observations have been made in kidneys collected from mice submitted for routine colony health monitoring, which have not undergone any experimental intervention [2]. Microbiology, parasitology, necropsy, histopathology, PCR and immunohistochemistry investigations have, to date, all failed to detect a pathogen that might be associated with these murine renal intranuclear inclusion bodies, and the tubular inclusions have so far been considered an idiopathic, degenerative lesion [2].

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