Analysis Tools
mortality/aging
|
• most mice die within a day or two of birth
|
|
• intercrosses of heterozygotes indicate a ~40% loss of homozygotes at weaning age; no deaths are observed during fetal development
|
growth/size/body
|
• after weaning, homozygotes develop into obese adults
• by 6 months of age, homozygotes are on an average 31% heavier than control littermates
|
|
• at P5 and P21, homozygotes are smaller than wild-type or heterozygous controls
|
|
• at P1 and P20, homozygotes show a significant reduction in body weight (36% and 20%, respectively) relative to wild-type controls
|
cardiovascular system
|
• at E16, all homozygotes show a reduction in myocardial tissue due to increased cell death in alpha-actinin-positive cardiomyocytes
|
|
• at E16, homozygotes show a marked reduction in the number of cardiomyocytes expressing sarcomeric alpha-actinin relative to wild-type controls
• a reduction in the number of alpha-actinin positive Z-bands is noted in both the ventricular wall and septum
• however, no difference is observed in the abundance of E16 alpha-smooth muscle actin positive cells
|
|
• at E16, Doppler color imaging revealed mixing of right and left ventricular blood flow due to lack of ventricular septum formation
|
|
• at 6 months of age, homozygotes exhibit thinning of the ventricular septum
• however, no incomplete ventricular septa are detected in adult hearts
|
|
• at E16, only about 50% of homozygotes (11 out 21) display a clearly observable ventricular septum defect
|
|
• at E13 and E16, homozygotes display increased apoptosis in alpha-actinin positive ventricular cardiomyocytes relative to controls, as shown by TUNEL analysis
• however, no changes in fetal cardiac cell proliferation or beta-catenin levels are observed
|
behavior/neurological
|
• homozygotes show a 10-fold decrease in the amount of time they are able to maintain their balance on the rotarod relative to wild-type controls
|
|
• homozygotes release their grip on the wire lid almost immediately, with an average hang time less than 1 sec versus 17 sec in wild-type controls
|
|
• homozygotes exhibit a wobbly gait
|
|
• neonatal homozygotes are less active than wild-type or heterozygous controls
|
muscle
|
• at E16, all homozygotes show a reduction in myocardial tissue due to increased cell death in alpha-actinin-positive cardiomyocytes
|
|
• at E13 and E16, homozygotes display increased apoptosis in alpha-actinin positive ventricular cardiomyocytes relative to controls, as shown by TUNEL analysis
• however, no changes in fetal cardiac cell proliferation or beta-catenin levels are observed
|
|
• at E16, mutant hearts display reduced numbers of alpha-actinin positive Z-bands in both the ventricular wall and septum
|
adipose tissue
|
• by 6 months of age, all homozygotes exhibit excess of adipose tissue relative to control littermates
|
cellular
|
• at E13 and E16, homozygotes display increased apoptosis in alpha-actinin positive ventricular cardiomyocytes relative to controls, as shown by TUNEL analysis
• however, no changes in fetal cardiac cell proliferation or beta-catenin levels are observed
|
integument
