Phenotypes associated with this allele

• Allele Symbol: Actn2^em1Kage
• Allele Name: endonuclease-mediated mutation 1, Katja Gehmlich
• Allele ID: MGI:7482516
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Actn2^em1Kage/Actn2^em1Kage	C57BL/6-Actn2^em1Kage	MGI:7482598
ht2	Actn2^em1Kage/Actn2^+	C57BL/6-Actn2^em1Kage	MGI:7482599

Genotype
MGI:7482598

hm1

• Allelic Composition: Actn2^em1Kage/Actn2^em1Kage
• Genetic Background: C57BL/6-Actn2^em1Kage

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:334092 )

• no homozygous offspring are obtained and E15.5 is the last time point that viable homozygotes are present

• however, gross morphology and size at E15.5 appears normal and no developmental delay is seen

cardiovascular system

abnormal pulmonary trunk morphology ( J:334092 )

• pulmonary trunk volume is reduced despite normal length

aorta stenosis ( J:334092 )

• aortic stenosis is seen in the ascending and descending thoracic aorta, but not in the aortic root

abnormal heart morphology ( J:334092 )

• reduction in the number of nuclei in hearts and they are rounder in shape

abnormal heart left atrium morphology ( J:334092 )

• E15.5 hearts show smaller left atrium volume

perimembraneous ventricular septal defect ( J:334092 )

• 3 of 8 E15.5 hearts have peri-membranous ventricular septal defects

decreased heart left ventricle wall thickness ( J:334092 )

• E15.5 hearts show reduced left ventricular free wall thickness

abnormal heart right ventricle morphology ( J:334092 )

• E15.5 hearts show increased right ventricle luminal volume

abnormal pulmonary valve morphology ( J:334092 )

• dysplastic pulmonary valves with thickened leaflets are seen

thick pulmonary valve cusps ( J:334092 )

• thickened pulmonary valve leaflets are seen, particularly in the right and left leaflets

abnormal fetal cardiomyocyte physiology ( J:334092 )

• dividing cells in E15.5 hearts show metaphase chromosome arrangement but with residual sarcomere structures indicating a defect in myofibril disassembly

decreased fetal cardiomyocyte proliferation ( J:334092 )

• E15.5 hearts show fewer cells that are positive for phosphorylated histone H3, a nuclear marker of active proliferation, indicating reduced proliferation

muscle

decreased fetal cardiomyocyte proliferation ( J:334092 )

• E15.5 hearts show fewer cells that are positive for phosphorylated histone H3, a nuclear marker of active proliferation, indicating reduced proliferation

abnormal sarcomere morphology ( J:334092 )

• sarcomere length is increased in cardiomyocytes

abnormal Z line morphology ( J:334092 )

• Z-disks appear less uniform in hearts and while Z-disk measurements show no difference in Z-disk width, the width distribution is much wider than in wild-type

cellular

decreased fetal cardiomyocyte proliferation ( J:334092 )

• E15.5 hearts show fewer cells that are positive for phosphorylated histone H3, a nuclear marker of active proliferation, indicating reduced proliferation

Genotype
MGI:7482599

ht2

• Allelic Composition: Actn2^em1Kage/Actn2⁺
• Genetic Background: C57BL/6-Actn2^em1Kage

cardiovascular system

cardiovascular system phenotype ( J:334092 )

N • young adult mice (3 months) and more mature mice older than 34 weeks of age exhibit normal cardiac function and dimensions and normal heart weight, indicating no overt cardiomyopathy phenotype

abnormal cardiovascular system physiology ( J:334092 )

♂ • while mice do not show an overt cardiomyopathy phenotype, males show induction of the fetal gene program at 38 weeks of age and induction of hypertrophic signaling transcripts in hearts, molecular features consistent with hypertrophic cardiomyopathy

muscle

muscle phenotype ( J:334092 )

N • skeletal muscle shows no signs of pathology