Figure 1.

Characterization of Spontaneous Obese Mice. (A, B) Some littermates displayed pronounced obesity and adiposity, which also manifested in increased mass of the liver, heart, kidney, and adipose tissue. (C, D) Obesity occurred between week 4 and 5 of age as a result of a marked increase in food intake. (E) Obesity was associated with hyperglycemia, hyperinsulinemia, increased leptin, but unaltered plasma NEFA concentrations. (F) In total, 36 nonsynonymous mutations were shared between two obese animals compared to one lean littermate, including 16 common mutations (occurring in >10 other species), 10 rare mutations (occurring in 2–5 other species), and 10 unique mutations (occurring in <2 other species). (G) The Cyfip2 gene appears to be a hotspot for mutations, including the S968F mutation and several others within the cytoplasmic fragile-X interacting, WAVE and Nap1 binding domains. Data expressed as mean ± SEM of results obtained from n = 3–10 for each genotype. *P < .05 versus lean (unpaired two-tailed Student’s t-test). Nap1, Nck-associated protein 1; NEFA, nonesterified fatty acids; WAVE, Wiskott–Aldrich syndrome protein–family verprolin-homologous protein.