International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 4 - A NOVEL POLYGENIC MOUSE MODEL OF OBESITY AND DIABETES: EVALUATION OF GENETIC AND NUTRITIONAL CONTROL OF OBESITY AND GLUCOSE HOMEOSTASIS

M. Dhar
University of Tennessee

1) Nelson S, 1) Kirkland T, 1) Sullivan CS, 1) Kim S, 2) Sommardahl C, 3) Nicholls RD, 1) Moustaid-Moussa N. and 1) Johnson DK.
1) Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN;  2) University of Tennessee College of Veterinary Medicine, Knoxville, TN; 3) Department of Psychiatry, University of Pennsylvania, Philadelphia, PA.

We have shown that a critical region of mouse chromosome 7, near the pink-eyed (p) dilution locus, coincides with QTLs for body weight and type 2 diabetes phenotypes.  Maternal inheritance of either of two radiation-induced p deletion mutations, p30Pub and p23DFiOD, results in a significant increase in body fat and hyperinsulinemia.  Physical mapping and sequence analysis of this region predicts a single transcript, Atp10c, encoding an ATPase that is a putative aminophospholipid translocase.  The human ortholog, ATP10C, which maps to the homologous region on chromosome 15q12 has also been characterized; amino acid sequences of the two genes are 85% and the overall genomic organization is conserved.  ATP10C maps to the Angelman syndrome (AS) critical region and may associate with a molecular subclass of AS patients with a BMI in the 80-100th percentile for age.  Atp10c is expressed in a variety of human and mouse tissues, including white abdominal adipose tissue.  Atp10c is down-regulated in vitro during differentiation from preadipocytes to adipocytes in the presence of insulin.  To gain insights into obesity and glucose homeostasis in these animals, and to study the biological role of Atp10c leading to these phenotypes, biochemical and molecular studies have been initiated.  Glucose and insulin tolerance tests of mutant and control mice on diets containing10% fat (kcal) are compared to those on 44% fat (kcal).  Atp10c expression profiles are also being generated using RT-PCR.  These data will help further our understanding of obesity and glucose homeostasis in this polygenic mouse model, with expected functional relevance to humans.


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