Phenotypes associated with this allele

• Allele Symbol: Casz1^tm1.1Flc
• Allele Name: targeted mutation 1.1, Frank Conlon
• Allele ID: MGI:5638931
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Casz1^tm1.1Flc/Casz1^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:5811817
cn2	Casz1^tm1.1Flc/Casz1^tm1.1Flc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:5811822
cn3	Casz1^tm1.1Flc/Casz1^tm1.1Flc Isl1^tm1(cre)Tmj/Isl1^+	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL	MGI:5811826
cn4	Casz1^tm1.1Flc/Casz1^tm1.1Flc Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA * SJL	MGI:5811819

Genotype
MGI:5811817

cn1

• Allelic Composition: Casz1^tm1.1Flc/Casz1⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

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

normal phenotype

no abnormal phenotype detected ( J:221324 )

• mice are viable, fertile and show no obvious phenotypic abnormalities

Genotype
MGI:5811822

cn2

• Allelic Composition: Casz1^tm1.1Flc/Casz1^tm1.1Flc; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:221324 )

• no viable embryos are identified after E14.5

• however, embryos appear grossly normal at E12.5

homeostasis/metabolism

edema ( J:221324 )

• severe edema at E13.5

cardiovascular system

thin myocardium ( J:221324 )

• severe thinning of the myocardium by E12.5

abnormal heart development ( J:221324 )

• abnormal heart development between E10.5 and E12.5

decreased fetal cardiomyocyte number ( J:221324 )

• at E12.5, the number of tropomyosin (TMY)-positive cardiomyocytes is significantly reduced in the ventricles

• however, no increase in programmed cell death is observed and actin filaments are intact

abnormal heart apex morphology ( J:221324 )

• heart fails to form an apex for either the left or the right ventricle

increased heart right atrium size ( J:221324 )

• enlarged right atrium at E12.5; more pronounced at E13.5

dilated heart right atrium ( J:221324 )

• ballooning of the right atria by E13.5, indicating blood pooling in the right ventricle

abnormal heart shape ( J:221324 )

• misshapen heart at E13.5

heart hypoplasia ( J:221324 )

• severe cardiac hypoplasia by E13.5

• at E12.5, cardiac hypoplasia is specific to cardiomyocytes and does not affect the epicardium or endothelial cells

abnormal heart ventricle morphology ( J:221324 )

• narrower ventricular lumens by E13.5

trabecula carnea hypoplasia ( J:221324 )

• decreased trabeculation at E12.5

abnormal interventricular septum morphology ( J:221324 )

• underdeveloped interventricular septum at E12.5

perimembraneous ventricular septal defect ( J:221324 )

• membranous ventricular septal defects by E13.5

abnormal heart left ventricle morphology ( J:221324 )

• malformed left ventricle at E12.5; more pronounced at E13.5

thin ventricular wall ( J:221324 )

• thinning of the ventricular walls starting at E12.5

distended pericardium ( J:221324 )

• inflated pericardial sacs at E13.5

hemorrhage ( J:221324 )

• severe blood hemorrhaging at E13.5

poor circulation ( J:221324 )

• decreased blood flow throughout the vasculature by E13.5

abnormal fetal cardiomyocyte physiology ( J:221324 )

• at E12.5, the G1-to-S phase progression of cardiomyocytes is impaired, as shown by a prolonged or arrested G1 phase, a reduction in DNA synthesis, an increase in phospho-RB, and a decrease in the cardiac mitotic index

decreased fetal cardiomyocyte proliferation ( J:221324 )

• cardiomyocyte proliferation is significantly reduced in E12.5 ventricles, as shown by EdU incorporation

cellular

decreased fetal cardiomyocyte proliferation ( J:221324 )

• cardiomyocyte proliferation is significantly reduced in E12.5 ventricles, as shown by EdU incorporation

abnormal cell cycle checkpoint function ( J:221324 )

• at E12.5, cell cycle profiling of cardiac nuclei revealed a significant increase of cells in G1 phase and a simultaneous decrease of cells in S phase, with no alteration in the % of cells in G2 phase

decreased mitotic index ( J:221324 )

• cardiomyocyte mitotic index is significantly reduced in E12.5 ventricles, as shown by phospho-histone H3 staining

muscle

trabecula carnea hypoplasia ( J:221324 )

• decreased trabeculation at E12.5

thin myocardium ( J:221324 )

• severe thinning of the myocardium by E12.5

decreased fetal cardiomyocyte proliferation ( J:221324 )

• cardiomyocyte proliferation is significantly reduced in E12.5 ventricles, as shown by EdU incorporation

Genotype
MGI:5811826

cn3

• Allelic Composition: Casz1^tm1.1Flc/Casz1^tm1.1Flc; Isl1^tm1(cre)Tmj/Isl1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:221324 )

• embryos are viable and indistinguishable from controls at least until E14.5; however, no mice are recovered postnatally

cardiovascular system

abnormal heart shape ( J:221324 )

• misshapen heart at E14.5

• however, no ventricular septal defects are detected at E14.5

abnormal heart right ventricle morphology ( J:221324 )

• right ventricular wall thickness is significantly reduced at E14.5

• however, left ventricular wall thickness is normal

heart right ventricle hypoplasia ( J:221324 )

• right ventricular hypoplasia at E14.5

cellular

decreased mitotic index ( J:221324 )

• at E12.5, cardiomyocyte mitotic index is significantly reduced in the right ventricles (but not in the left ventricles), as shown by phospho-histone H3 staining

Genotype
MGI:5811819

cn4

• Allelic Composition: Casz1^tm1.1Flc/Casz1^tm1.1Flc; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:221324 )

• embryos do not survive past E14.5

cardiovascular system

abnormal heart development ( J:221324 )

• at E12.5, embryos show a cardiac phenotype indistinguishable from that of embryos homozygous for Casz1^tm1.1Flc and heterozygous for Nkx2-5^tm1(cre)Rjs

ventricular septal defect ( J:221324 )

• at E12.5

heart hypoplasia ( J:221324 )

• severe cardiac hypoplasia at E12.5

thin ventricular wall ( J:221324 )

• at E12.5