Submitted on September 23, 2008
Revised on February 25, 2009
Accepted on March 10, 2009
New Zealand Ginger Mouse: Novel model that associates the tyrp1b pigmentation gene locus with regulation of lean body mass
Cecile E. Duchesnes1, Jurgen K Naggert2, Michele A Tatnell1, Nikki Beckman1, Rebecca N Marnane1, Jessica Astrid Rodrigues1, Angela Halim1, Beau Pontre1, Alistair W Stewart1, George L. Wolff3, Robert Elliott1, and Kathleen G Mountjoy1*
1 University of Auckland
2 The Jackson Laboratory
3 National Center for Toxicological Research
* To whom correspondence should be addressed. E-mail: kmountjoy{at}auckland.ac.nz.
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 coloured 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 exhibits a semi-dominant 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 (oca2p and tyrp-1b) and that the tyrp-1b gene locus associates with large body size. Three coat colours appeared in the N2 generation; ginger, brown and dark. Strikingly, N2 male coat colour associated with body weight; the brown coloured mice weighed the heaviest followed by ginger and then dark. The male brown coat coloured 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.
