Mouse Genome Informatics
hm
    Leprdb/Leprdb
C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes subjected to 30, 45, and 60 min of left coronary artery ischemia-reperfusion exhibit survival rates of 71%, 53%, and 18%, respectively, at 24 h after reperfusion, much lower than in controls
• homozygotes subjected to 30 and 45 min of left coronary artery occlusion show survival rates of 58% and 44%, respectively, at 28 days after reperfusion, compared to 100% and 88% in controls

behavior/neurological

endocrine/exocrine glands
• islet mass and density are significantly increased compared to wild-type mice
• individual beta cell size is increased

growth/size/body
• overweight by 4 weeks of age

homeostasis/metabolism
• homozygotes subjected to 45 min of ischemia display an increase in diastolic dimensions, significant dilatation of left ventricular end-systolic dimensions, a 30% reduction in fractional shortening, and an increase in cardiac hypertrophy, 28 days postreperfusion, indicating decreased tolerance to myocardial infarction
• significant increase in the percentage of plasma glycosylated hemoglobin
• diabetic phenotype appears earlier in males than in females
• by 8 weeks (J:106597)
• hyperinsulinemia by 8 weeks (J:106597)

cardiovascular system
• myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age
• at low fatty acid supply, hearts consume 86% more oxygen (MVO2) for noncontractile purposes compared with control hearts and a further increase in fatty acid supply has no effect on the already elevated unloaded MVO2, indicating reduced cardiac efficiency in unloaded hearts (J:106871)
• reduced aortic flow
• cardiac output is reduced in fatty acid perfused hearts (J:106871)
• reduced recovery of mechanical function after 13 minutes of ischemia and reperfusion
• hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin
• hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia
• maximal contractions increase with age rather than decrease as in controls
• hearts show a significant increase in the slope of the MVO2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency
• hearts show a significant increase in the slope of the MVO2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency
• intrinsic heart rates are reduced at all workloads (J:106871)
• decreased peak systolic pressure
• decreased peak systolic pressure X cardiac output
• decreased peak systolic pressure X heart rate
• homozygotes subjected to 45 min of ischemia display an increase in diastolic dimensions, significant dilatation of left ventricular end-systolic dimensions, a 30% reduction in fractional shortening, and an increase in cardiac hypertrophy, 28 days postreperfusion, indicating decreased tolerance to myocardial infarction

hematopoietic system
• significant increase in the percentage of plasma glycosylated hemoglobin

cellular
• elevation of fatty acids in perfused hearts causes an increase in fatty acid oxidation combined with a reduction in glucose oxidation rates (J:106871)
• carbohydrate oxidation becomes reduced (J:107138)
• palmitate oxidation is elevated (J:107138)
• state 3 respiration is elevated in cardiac mitochondria incubated with palmitoyl-carnitine but not with pyruvate

muscle
• hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin
• hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia
• maximal contractions increase with age rather than decrease as in controls
• hearts show a significant increase in the slope of the MVO2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:104790
Obesity 601665 J:96047 , J:104790 , J:106871