Mouse Genome Informatics
ot
    Htr2ctm1Jul/Y
B6.129S-Htr2ctm1Jul
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• both young (12-14 weeks) and older (39-43 weeks) male hemizygotes show a significant increase in daily food intake relative to wild-type controls
• however, no significant differences are observed in plasma glucose, corticosterone, triglycerides or FFAs at either age
• hemizygotes show reduced aversion to a novel environment; the latencies to emerge from a small dark enclosure into a brightly lit open field are reduced in mutants compared to wild-type
• hemizygotes show abnormal performance in the Morris water maze, failing to show a preference for the trained site in probe trials following training
• however, contextual conditioning is normal

adipose tissue
• on a standard chow diet, male hemizygotes show an age-dependent increase in white adipose tissue (WAT) deposits relative to wild-type controls
• at 39-43 weeks of age, epididymal, perirenal and subcutaneous WAT weights are increased by 40-64% relative to wild-type levels
• at 39-43 weeks of age
• at 39-43 weeks of age

growth/size/body
• on a standard chow diet, male hemizygotes develop late onset obesity at >20 weeks of age
• by 42 weeks of age, hemizygotes show a ~30% increase in body weight relative to wild-type controls
• when fed a high-fat diet for 9 weeks, male hemizygotes display a significantly higher gain weight than similarly treated wild-type mice; however, no differences in plasma FFA or triglyceride levels are observed

homeostasis/metabolism
• when fed a high-fat diet for 9 weeks, male hemizygotes display a significantly higher gain weight than similarly treated wild-type mice; however, no differences in plasma FFA or triglyceride levels are observed
• when fed a high-fat diet for 9 weeks, male hemizygotes display plasma glucose levels in the diabetic range (>300 mg/dl); however, no hyperlipidemia is observed
• at 39-43 weeks of age, male hemizygotes display a 7-fold increase in plasma insulin levels relative to wild-type controls; however, plasma insulin levels are normal at 12-14 weeks of age
• when fed a high-fat diet for 9 weeks, male hemizygotes display hyperinsulinemia relative to similarly treated wild-type mice
• at 39-43 weeks of age, male hemizygotes display a 2.5-fold increase in plasma leptin levels relative to wild-type controls; however, plasma leptin levels are normal at 12-14 weeks of age
• when fed a high-fat diet for 9 weeks, male hemizygotes display hyperleptinemia relative to similarly treated wild-type mice
• at 120 min after a single i.p. injection of D-glucose (1 gm/kg), obese male hemizygotes display significantly higher blood glucose levels than wild-type controls, indicating impaired glucose tolerance
• after a 6 hr fast, 42-58 week old (obese) male hemizygotes show both hyperinsulinemia and mildly increased blood glucose levels, indicating insulin resistance
• obese hemizygotes display markedly increased white adipose tissue TNF mRNA levels, despite normal plasma FFA and corticosterone levels
• following an i.p. injection of 2.5 mg/kg of leptin, 38-46 week old male hemizygotes mice exhibit a smaller decrease in food intake and body weight relative to wild-type controls; however, leptin resistance can be overcome by a higher dose (5 mg/kg) and is therefore only partial in obese hemizygotes
• no differences in the effects of either leptin dose (2.5 or 5 mg/kg) on food intake and body weight are observed in younger male hemizygotes at 11-13 weeks of age

nervous system
• selective impairment of long-term potentiation restricted to medial perforant path-dentate gyrus synapses of mutants, indicating perturbed dentate gyrus function

immune system
• obese hemizygotes display markedly increased white adipose tissue TNF mRNA levels, despite normal plasma FFA and corticosterone levels

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:50262