Background and Purpose: Phenotype assessment of genetically modified rodents is an essential component of animal model development and their eventual use. Described here is a paradigm to consider as we collectively pursue phenotype assessment of the constantly increasing number of genetically modified rodent models, as well as those with spontaneously occurring mutations. Methods: Review of past experiences and the literature provides useful examples to illustrate the principles described. Conclusion: A practical approach to phenotype assessment can be divided into a primary level of assessment to find abnormalities, and a secondary level of more specialized assessment to quantify and evaluate the abnormalities detected. There are many subtle, but important phenotypic characteristics that can be markedly affected by the background genetics and environment of the animal being assessed.

Background and Purpose: Colorectal cancer (CRC) remains one of the most common cancer forms developing in industrialized countries, and its incidence appears to be rising. Studies of human population groups provide insufficient information about carcinogenesis, pathogenesis, and treatment of CRC. To study these phenomena in detail, a number of animal models of human CRC have been developed. The hypothetical ideal animal model should mimic the human disease in terms of morphology, biochemical alterations, and biological behavior. No existing model replicates the disease as an entity, but available models approximate many of the characteristics of human colonic carcinogenesis and metastasis. So far few comparative evaluations of the various animal models of CRC have been made. Conclusion: Animal studies cannot replace human clinical trials, but they can be used as a pre-screening tool, so that human trials become more directed, with greater chances of success. The orthotopic transplantation of colon cancer cells into the cecum of syngeneic animals or intraportal inoculation appears to resemble the human metastatic disease most closely, providing a model for study of the treatment of metastases. Which model(s) to choose depends on the goal(s) of the experiment(s). The review published here can provide help in selecting the most optimal CRC model(s) for a certain purpose and in preventing unnecessary duplication of animal experimentation.

Background and Purpose: The Td^ho allele is an X-linked dominant, embryonic male-lethal mouse mutation that occurs between embryonic day (E) 12.5 and E14.5. The lethal cause and responsible gene have not been identified until now. The cause of lethality in Td^ho male embryos was examined with respect to the defect of hematopoiesis. Methods: Suppression subtractive hybridization and Northern blot analysis were performed on E12.5 male Td^ho and normal mouse embryos. In addition, histochemical examinations and blood cell counts of normal and mutant E12.5 embryos were carried out. Results: Diminished expression of embryonic globin genes (and globins) in the blood of E12.5 Td^ho male embryos were documented by use of Northern blot analysis and subtractive hybridization. Increased apoptosis of yolk sac-derived erythrocytes was found in E12.5 Td^ho male embryos. Furthermore, diminished numbers of anucleated erythrocytes were observed in E12.5 mutant embryos. Conclusions: A defect of embryonic hematopoiesis in Td^ho mice was suggested as one of the possible causes of embryo lethality.

Background and Purpose: Regional variations in the intraepithelial lymphocytes (IELs) in the mouse small intestine were examined. Methods: The small intestine was taken from six 12-week-old BALB/c mice and divided equally into three parts (proximal, middle, and distal). The IELs were isolated from each part of the intestine and analyzed by use of flow cytometry. Results: The number of IELs in the distal part of the small intestine was significantly lower than that in the proximal and middle parts (P < 0.01). The distribution of IEL subsets was markedly different between the proximal and the distal parts, and that in the middle part had an intermediate pattern. The percentage of T cells and expression of Thy-1.2 on the T and T cells were higher in the distal part (P < 0.01). The percentage of CD8 and of double-negative T cells were higher in the proximal part, whereas that of CD4CD8 double-positive T cells was higher in the distal part (P < 0.01). Regional variations were found mainly in the extrathymically developed T cell subsets. Conclusion: Local development of IELs may differ between regions of the small intestine.

Background and Purpose: The clinical presentation, diagnosis, histopathologic findings, and elimination of dual respiratory tract infection with Pasteurella pneumotropica and Pneumocystis carinii were studied in 100 adult barrier-reared C. B17 and MRL- lpr mice homozygous for a targeted mutation of the J_H region of the immunoglobulin heavy chain. Methods: Necropsy, aerobic bacteriologic culture of hematogenous and pulmonary tissues, histochemical staining of pulmonary tissues, polymerase chain reaction analysis of pulmonary tissues and feces, and viral serologic testing were performed on 19 clinically affected mice and 8 clinically normal mice, then later on antibiotic-treated and caesarian re-derived mice. Therapeutic strategies included sequential administration of trimethoprim/ sulfamethoxazole and enrofloxacin or enrofloxacin administration and caesarian rederivation. Results: Clinically affected mice had diffuse, nonsuppurative, interstitial pneumonia with superimposed pyogranulomatous lobar pneumonia that was detected microscopically. Affected lung tissue yielded pure culture of P. pneumotropica. Aged-matched, clinically normal mice of both genotypes had interstitial histiocytic pneumonia without lobar pneumonia, and P. pneumotropica was not isolated. Histochemical staining of lung tissues from normal and clinically affected mice revealed scattered cysts consistent with P. carinii, principally in the interstitium. Treatment with sulfamethoxazole/trimethoprim and enrofloxacin eliminated bacteriologic detection of P. pneumotropica, decreased mortality from 50% to 6%, and improved breeding performance. Conclusion: A successful antibiotic therapy and rederivation approach, incorporating enrofloxacin, cesarian section, and isolator rearing, was developed for B cell-deficient mice with opportunistic infections.

Background and Purpose: Callitrichids (marmosets and tamarins) are extremely susceptible to experimental tumor induction by herpesviruses native to other primate species. A colony of common marmosets developed a syndrome of weight loss, inappetence, diarrhea, and in several animals, palpable abdominal masses. Methods: Marmosets in the colony were subjected to histologic examination and serologic testing for EpsteinBarr virus (EBV). The DNA from tumors that developed in the marmosets was subjected to consensus primer polymerase chain reaction (PCR) analysis designed to amplify conserved regions of herpesvirus genomes. Results: The mesenteric lymph nodes and intestinal mucosa were consistently infiltrated by principally B lymphocytes, which often obliterated the normal architecture. Of 84 clinically normal marmosets, 52 were seropositive for EBV. The tumor DNA contained previously unreported herpesvirus sequences closely related to but distinct from those of EBV, Herpesvirus papio, and these lymphocryptovirus, a novel gammaherpesvirus. Results of PCR analysis of circulating lymphocytes from EBV-positive, clinically normal marmosets were negative for EBV antibodies and were positive for marmoset lymphocryptovirus; PCR analysis of circulating lymphocytes from EBVnegative marmosets yielded negative results for EBV and this novel marmoset lymphocryptovirus. Conclusion: This novel gammaherpesvirus possibly associated with tumor development may have important management implications for captive callitrichids.