Mice that are homozygous for this knockout are viable, fertile, and exhibit a smaller stature and increased locomotor activity when compared to wildtype controls. No gene product (mRNA or protein) is detected by RT-PCR and in situ hybridization analysis of hypothalamus tissue, RT-PCR of pancreatic islets from homozygotes and immunocytochemical analysis of brain tissue from homozygotes.
Homozygotes appear smaller, are leaner than wildtype controls and when placed on a chow diet, display increased basal metabolic rates and locomotor activity.
When fed a high-fat diet, the oxygen consumption ( by 15.7%) and activity levels are further increased and homozygotes do not gain as much weight as controls. The lean phenotype persists in homozygous mice more than 12 months of age. Homozygotes, 12-19 months of age, are more sensitive to insulin, have reduced aging-associated weight and visceral adiposity gain, maintain increased locomotor activity, and are resistant to aging-associated glucose intolerance. Pancreas tissue from homozygotes have smaller islets and decreased beta cell mass. Homozygotes fed a high fat diet do not exhibit the increase in beta cell mass observed in wildtype controls. Homozygotes have shorter sleep periods (increased wakefulness), and under fasting conditions exhibit accelerated weight loss and reduced REM sleep. The Donating Investigator reports that homozygous females have reduced litter size and pup survival.
