Abstract
Meriones unguiculatus (Mongolian gerbil) may be useful for studying some aspects of prostate gland biology. The prostate gland of the gerbil is more compact than that of rodents, and the tissues respond to hormone treatment. In this study the investigators analyzed prostates from aging gerbils to determine the incidence and spectrum of age-related changes. Thirty 18 month old gerbils were examined and histopathologic lesions were found in 80% of these. The most frequent alteration was prostatic intraepithelial neoplasia (PIN) which was present in 14/30 gerbils, while invasive carcinoma and adenocarcinoma were found in 8/30 animals. Hyperplasia of the stromal cells was seen in 6/30 animals, and was always associated with epithelial lesions. Light microscopic findings were confirmed by ultrastructure examination. Quantitative analysis revealed that indices of proliferation and cell death were positively correlated with the more aggressive lesions, and microinvasive carcinomas had the highest proliferative index. The authors conclude that old gerbils have a high rate of spontaneous prostatic lesions and could be a good model for human PIN.
Campos SG, Zanetoni C, Scarano WR, Vilamaior PS, Taboga SR. Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disorders. Int J Exp Pathol
Leptin is important in regulating energy homeostasis and food intake. Two mouse strains used to study the effects of leptin are the ob/ob mice which lack functional leptin, and db/db mice which lack leptin receptors. These mice are markedly obese but also display defects in innate and adaptive immunity. To determine the effects of leptin on hematopoiesis, Claycombe and colleagues compared the bone marrow compartment of ob/ob mice to C57BL/6 controls. Using flow cytometric analyses they found that ob/ob mice had only 60% as many nucleated cells in the bone marrow as the controls. There was a dramatic reduction in the B cell compartment, with only ob/ob mice having 70% fewer cells than C57BL/6. This was most apparent in reduced numbers of pre-B and immature B cells. Absolute numbers of granulocytes and monocytes were also reduced. Treatment of the mice with recombinant leptin for 12 days restored the marrow populations to near normal levels. These results support a role for leptin in lymphopoiesis and myelopoiesis and help explain the immune deficits previously observed in the ob/ob mouse.
Claycombe K, King LE, Fraker PJ. A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci USA
The laboratory rat is widely used to study mammary carcinogenesis, but different strains show a marked variation in their susceptibility to spontaneous and carcinogen-induced mammary neoplasms. The Copenhagen rat is resistant to mammary carcinogenesis while most other inbred rat strains are highly susceptible. Investigators performed microarray expression profiling on normal mammary tissue from pubescent female rats of various strains to determine differences in gene expression that might be responsible for strain susceptibility. Compared with the resistant Copenhagen strain, expression profiles from the susceptible strains all showed high levels of mRNA for prolactin, prolactin receptors, prolactin-regulated genes, and genes involved in the Jak-STAT pathway. To further investigate the potential role of prolactin in mediating mammary cancer resistance, Copenhagen rats were treated with perphenazine to elevate serum prolactin levels. This resulted in formation of mammary tumors when the treated rats were exposed to N-nitroso-N-methylurea. These findings indicate that deregulation of prolactin signaling plays a role in the differential susceptibility to mammary carcinogenesis in rats.
Ren X, Zhang X, Kim AS, et al. Comparative genomics of susceptibility to mammary carcinogenesis among inbred rat strains: role of reduced prolactin signaling in resistance of the Copenhagen strain. Carcinogenesis
Chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes are deficient in NAPDH oxidase activity. This results in the inability of phagocytes to generate reactive oxygen species, especially superoxide, and the affected individual suffers from recurrent bacterial and fungal infections. Paradoxically, CDG patients also have chronic inflammatory conditions and formation of multiple granulomas. The pathogenesis of this response was unclear. Using CDG mice infected with Aspergillus fumigatus, researchers determined that tryptophan catabolism is defective in these animals. A block in a superoxide-dependent step along the kynurenine pathway of tryptophan metabolism appears responsible for many of the manifestations of CDG. A better understanding of this mechanism may lead to improved therapy involving kynurenine replacement.
Romani L, Fallarino F, De Luca A. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature
Dendritic cells (DCs) are a critical component of the immune system and are being heavily studied in tumor vaccines and cancer immunotherapy. Canine transmissible venereal tumor (TVT) is able to evade the host's immune response initially, but tumors often regress over time due to alterations in immune function. This group investigated changes in monocyte-derived DCs during progression and regression of TVT. They found downregulation of several important surface molecules, decreased endocytic activity of immature DCs, a 40% decrease in circulating monocytes, and defects in DC maturation. Exposure to supernatants from TVTs cultured during the progression phase resulted in monocyte and DC death. During spontaneous regression, monocyte and DC parameters returned to normal. TVT appears to be a good model for investigating the immunologic interactions between tumor cells and the host.
Liu CC, Wang YS, Lin CY. Transient downregulation of monocyte-derived dendritic-cell differentiation, function, and survival during tumoral progression and regression in an in vivo canine model of transmissible venereal tumor. Cancer Immunol Immunother