New Zealand Ginger mouse: novel model that associates the tyrp1b pigmentation gene locus with regulation of lean body mass.

The study of spontaneous mutations in mice over the last century has been fundamental to our understanding of normal physiology and mechanisms of disease. Here we studied the phenotype and genotype of a novel mouse model we have called the New Zealand Ginger (NZG/Kgm) mouse. NZG/Kgm mice are very large, rapidly growing, ginger-colored mice with pink eyes. Breeding NZG/Kgm mice with CAST/Ei or C57BL/6J mice showed that the ginger coat colour is a recessive trait, while the excessive body weight and large body size exhibit a semidominant pattern of inheritance. Backcrossing F1 (NZG/Kgm x CAST/Ei) to NZG/Kgm mice to produce the N2 generation determined that the NZG/Kgm mouse has two recessive pigmentation variant genes (oca2(p) and tyrp-1(b)) and that the tyrp-1(b) gene locus associates with large body size. Three coat colors appeared in the N2 generation; ginger, brown, and dark. Strikingly, N2 male coat colour associated with body weight; the brown-colored mice weighed the most followed by ginger and then dark. The male brown coat-colored offspring reached adult body weights indistinguishable from NZG/Kgm males. The large NZG/Kgm mouse body size is a result of excessive lean body mass since these mice are not obese or diabetic. NZG/Kgm mice exhibit an unusual pattern of fat distribution; compared with other mouse strains they have disproportionately higher amounts of subcutaneous and gonadal fat. These mice are susceptible to high-fat diet-induced obesity but are resistant to high-fat diet-induced diabetes. We propose NZG/Kgm mice as a novel model to delineate gene(s) that regulate 1) growth and metabolism, 2) resistance to Type 2 diabetes, and 3) preferential fat deposition in the subcutaneous and gonadal areas.