Abstract
Purebred dogs are inbred and often carry genetic mutations that cause breed-specific diseases. In certain instances this makes purebred dogs good models for the human diseases. Such is the case with autosomal recessive neuronal ceroid lipofuscinosis (NCL) of the Border collie dog in Australia. As a group, NCLs are the most common neurodegenerative disorder found in children. Melville and colleagues studied NCL in Border collies and identified a nonsense mutation in exon 4 of the CLN5 gene. The CLN5 gene encodes a soluble lysosomal glycoprotein, and the mutation identified in this study results in a truncated protein. The authors have developed a DNA test for the mutation, which should be helpful in identifying carriers and developing a strategy for selective breeding.
Melville SA, Wilson CL, Chiang CS, Studdert VP, Lingaas F, Wilton AN. A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics
The health benefits of plant-derived phytoestrogens have been the subject of numerous investigations in humans in the past several years, but the role of dietary phytoestrogens on rodent uterine physiology has not been well characterized. Wang et al studied the effects of two commercial rodent chows, one with low phytoestrogen levels and one with high phytoestrogen levels, on uterine growth, estrogen-responsive gene expression and timing of implantation in CD1 mice. Compared with the low phytoestrogen diet, the diet with high phytoestrogens resulted in increased uterine growth, altered estrogen-responsive gene expression, and advancement in the timing of implantation. These findings have important implications for investigators using rodents to study the many physiologic and pathologic processes that can be influenced by estrogenic compounds.
Wang H, Tranguch S, Xie H, Hanley G, Das SK, Dey SK. Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus. Proc Natl Acad Sci USA
Canine cutaneous mast cell tumors (MCTs) are frequently encountered in veterinary practice, and it is not always possible to predict the biological behavior of these tumors based on histologic grade. Kiupel and colleagues examined 100 MCTs for tumor depth, tumor location and the presence of multiple tumors to determine if these parameters had prognostic significance. Dogs with multiple synchronous tumors had a worse prognosis than dogs with only a single tumor. Boxers and older dogs were more likely to develop MCTs at additional sites, while older dogs and male dogs had shorter survival compared to the rest of the group. The depth of the tumor, assessed by routine histologic examination, had no prognostic significance.
Kiupel M, Webster JD, Miller RA, Kaneene JB. Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours. J Vet Med A
Hereditary hemochromatosis (HH) is an iron-overload disorder and one of the most common genetic diseases in the United States. Mutations in five genes, including hemojuvelin (HJV), have been linked to HH but the exact role of these genes in normal and disease states is not entirely clear. Huang et al developed a mouse with homozygous disruption of the hemojuvelin gene. Hjv−/− mice had markedly increased iron deposition in the liver, pancreas and heart, with concurrent decreased iron levels in macrophages and decreased Hepcidin expression in target tissues—all features of human HH. Immunohistochemistry demonstrated increased ferroportin expression in intestinal epithelia and macrophages, leading the investigators to hypothesize that upregulated ferroportin activity is responsible for increased intestinal iron absorption and increased plasma iron levels. This new mouse model suggests that Hjv is a key regulator of iron homeostasis and provides a novel tool for the study of HH.
Huang FW, Pinkus JL, Pinkus GS, Fleming MD, Andrews NC. A mouse model of juvenile hemochromatosis. J Clin Invest
Long-term proliferation of mammalian epidermal stem cells is critical for the maintenance of normal epidermis. Self-renewing epidermal stem cells undergo terminal differentiation to form the interfollicular epidermis, sebaceous glands and hair follicles. Several factors, including an integrin component and a cytoskeletal component, are thought to be critical for maintaining the stem cell pool. A team led by Salvador Benitah developed a mouse which lacks Rac1 expression in the epidermis. Rac1 is a Rho guanosine triphosphatase involved in a diverse array of cellular processes. Deletion of Rac1 expression in the epidermis of adult mice resulted in rapid depletion of epidermal stem cells, possibly through loss of Rac1-mediated negative regulation of c-Myc. This model will be very useful for studying normal stem cell biology and for elucidating the role of Rac1 and c-Myc in epithelial tumors.
Benitah SA, Frye M, Glogauer M, Watt FM. Stem cell depletion through epidermal deletion of Rac1. Science