Phenotypes Associated with This Genotype

Genotype
MGI:5661554

• Allelic Composition: Ppp2r5c^{Gt(XP0444)Wtsi}/Ppp2r5c^{Gt(XP0444)Wtsi}
• Genetic Background: B6.129P2-Ppp2r5c^{Gt(XP0444)Wtsi}

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, incomplete penetrance ( J:210365 )

• most mice die within a day or two of birth

postnatal lethality, incomplete penetrance ( J:210365 )

• intercrosses of heterozygotes indicate a ~40% loss of homozygotes at weaning age; no deaths are observed during fetal development

growth/size/body

obese ( J:210365 )

• after weaning, homozygotes develop into obese adults

• by 6 months of age, homozygotes are on an average 31% heavier than control littermates

decreased body size ( J:210365 )

• at P5 and P21, homozygotes are smaller than wild-type or heterozygous controls

decreased body weight ( J:210365 )

• at P1 and P20, homozygotes show a significant reduction in body weight (36% and 20%, respectively) relative to wild-type controls

cardiovascular system

thin myocardium ( J:210365 )

• at E16, all homozygotes show a reduction in myocardial tissue due to increased cell death in alpha-actinin-positive cardiomyocytes

decreased fetal cardiomyocyte number ( J:210365 )

• 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

abnormal interventricular septum morphology ( J:210365 )

• at E16, Doppler color imaging revealed mixing of right and left ventricular blood flow due to lack of ventricular septum formation

thin interventricular septum ( J:210365 )

• at 6 months of age, homozygotes exhibit thinning of the ventricular septum

• however, no incomplete ventricular septa are detected in adult hearts

ventricular septal defect ( J:210365 )

• at E16, only about 50% of homozygotes (11 out 21) display a clearly observable ventricular septum defect

increased fetal cardiomyocyte apoptosis ( J:210365 )

• 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

impaired balance ( J:210365 )

• 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

decreased grip strength ( J:210365 )

• 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

abnormal gait ( J:210365 )

• homozygotes exhibit a wobbly gait

decreased locomotor activity ( J:210365 )

• neonatal homozygotes are less active than wild-type or heterozygous controls

muscle

thin myocardium ( J:210365 )

• at E16, all homozygotes show a reduction in myocardial tissue due to increased cell death in alpha-actinin-positive cardiomyocytes

increased fetal cardiomyocyte apoptosis ( J:210365 )

• 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

abnormal Z line morphology ( J:210365 )

• at E16, mutant hearts display reduced numbers of alpha-actinin positive Z-bands in both the ventricular wall and septum

adipose tissue

increased total body fat amount ( J:210365 )

• by 6 months of age, all homozygotes exhibit excess of adipose tissue relative to control littermates

cellular

increased fetal cardiomyocyte apoptosis ( J:210365 )

• 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

pallor ( J:210365 )

• at birth, homozygotes appear paler than control littermates