Analysis Tools
behavior/neurological
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• 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
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• 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
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polyphagia
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J:50262
)
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• 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
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adipose tissue
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• 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
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• at 39-43 weeks of age
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• at 39-43 weeks of age
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growth/size/body
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• 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
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• 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
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homeostasis/metabolism
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• 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
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hyperglycemia
(
J:50262
)
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• 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
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• 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
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• 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
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• 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
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• after a 6 hr fast, 42-58 week old (obese) male hemizygotes show both hyperinsulinemia and mildly increased blood glucose levels, indicating insulin resistance
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• obese hemizygotes display markedly increased white adipose tissue TNF mRNA levels, despite normal plasma FFA and corticosterone levels
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• 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
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nervous system
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• selective impairment of long-term potentiation restricted to medial perforant path-dentate gyrus synapses of mutants, indicating perturbed dentate gyrus function
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immune system
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• obese hemizygotes display markedly increased white adipose tissue TNF mRNA levels, despite normal plasma FFA and corticosterone levels
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| type 2 diabetes mellitus | DOID:9352 |
OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036 |
J:50262 | |
