Intercurrent Infections in Genetically Engineered Mice

Abstract

The laboratory mouse was domesticated from fancy mice that arose from geographically diverse genetic origins. The diverse origins of the mouse also contributed to a lengthy list of infectious agents that are carried by mice. Despite years of microbial quality control, the burgeoning use of mice for research is causing a resurgence of infectious disease among laboratory mice. Infections can be introduced through mice, but also through biologic products such as serum, hybridomas, and transplantable tumors and through iatrogenic introduction by scientists. Retroviruses represent an important group of agents with significant effects upon mouse research, but the transmissible exogenous viruses are no longer an issue among laboratory mice. The diversity of other infectious agents induce a wide variety of effects upon cancer research, including immunomodulation, tumor graft rejection, misinterpretation of phenotype, modified carcinogenesis, and zoonotic risk. Prudent research practices require that microbial status of research mice does not necessarily have to be standardized among laboratories, but it must be defined so that research results are reproducible and valid.

Microbial and Histopathologic Considerations in the Use of Mouse Models of Inflammatory Bowel Diseases

“…Here it is important to be aware that it is characteristic of mouse colonic mucosa that epithelial hyperplasia is accompanied by a tendency for proliferating crypt epithelium to penetrate the muscularis mucosa where inflammation is severe or prolonged, such as that often associated with Helicobacter spp. 66 (Fig. 3).…”

“…The proliferating and invading epithelium can appear quite dysplastic, making such lesions difficult to distinguish from early invasive carcinoma. 66,67 For studies in which cancer development is of interest, reference to published criteria for distinguishing such lesions from carcinoma 67 may be helpful. In addition to the problem that the method of histopathologic assessment may not be clearly presented, it may not be possible for the reader to independently assess the reported disease manifestations because they are not adequately illustrated.…”

‘One medicine—one pathology': are veterinary and human pathology prepared?

“…infections in immunologically impaired mice. 52,[54][55][56] Ample evidence has been published that these gastrointestinal lesions, including crypt herniation through the smooth muscle, disappear with antibiotic treatment. 54,57 However, some authors have persisted in naming these dysplasias of repair as 'non-metastatic carcinomas'.…”

“…54,57 However, some authors have persisted in naming these dysplasias of repair as 'non-metastatic carcinomas'. 55 Enthusiastic, but premature, reports of 'simultaneous transformation' of mammary epithelium induced by oncogenes is another example that led investigators to assume that the 'tumors' were malignant. 58 However, the test-by-transplantation proved the 'tumors' to be premalignant.…”