Phenotypes associated with this allele

• Allele Symbol: Creld1^{tm1c(EUCOMM)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:7522336
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6N * SJL	MGI:7546787
cn2	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Tg(CMV-cre)1Cgn/?	involves: BALB/cJ * C57BL/6 * C57BL/6N * SJL	MGI:7546785
cn3	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * C57BL/6N * SJL	MGI:7546786
cn4	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6N * FVB/N * SJL	MGI:7546788

Genotype
MGI:7546787

cn1

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6N * SJL

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

normal phenotype

no abnormal phenotype detected ( J:304446 )

• mice are recovered at Mendelian ratios at 3 weeks of age and do not exhibit an overt cardiac phenotype

Genotype
MGI:7546785

cn2

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Tg(CMV-cre)1Cgn/?
• Genetic Background: involves: BALB/cJ * C57BL/6 * C57BL/6N * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:304446 )

• homozygous embryos are present at Mendelian ratios at E10.0-E10.5 but die soon after; no viable homozygotes are recovered after E11.5

Genotype
MGI:7546786

cn3

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N * SJL

normal phenotype

no abnormal phenotype detected ( J:304446 )

• mice are born in Mendelian ratios and survive to adulthood with no gross phenotype; despite a slight reduction in left ventricular diastolic diameter, overall heart development and function are normal

Genotype
MGI:7546788

cn4

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/N * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:304446 )

• a few homozygotes survive to P13; no viable homozygotes are recovered at weaning age

neonatal lethality, incomplete penetrance ( J:304446 )

• although viable homozygous embryos are present at Mendelian ratios at E10.5 and E13.5, most homozygotes die shortly after birth due to heart failure

growth/size/body

decreased body size ( J:304446 )

decreased body weight ( J:304446 )

• at P0-P13, body weight is significantly lower than in control littermates

cardiovascular system

abnormal trabecula carnea morphology ( J:304446 )

• at E13.5, trabeculae are morphologically distinct and not yet compacting

• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae

ventricle myocardium hypoplasia ( J:304446 )

• at P0, P5 and P7, ventricles show myocardial hypoplasia

abnormal heart development ( J:304446 )

• transcriptome analysis shows altered transcriptional networks in both atria and ventricles at P3

• at E13.5, hearts show extracellular matrix (ECM) remodeling, as indicated by increased expression of Fn1 (fibronectin 1) and Lamb3 (laminin, beta 3)

• at E13.5, surface expression of Jag1 (jagged 1) on myocardial (Vcam1+) cells is reduced, leading to altered Notch1 signaling and heart development

• however, no defects in proliferation are noted in the atria or ventricles and no increased cell death is detected at E13.5

increased heart atrium size ( J:304446 )

• at P0, P5 and P7, atria are severely enlarged

cardiac fibrosis ( J:304446 )

• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae

• the fibrotic area is significantly increased in both the atria and ventricles relative to control mice

cardiovascular shunt ( J:304446 )

• at E13.5, mice exhibit an intraventricular shunt (IVS), whereas ventricles are already fully septated in control embryos

congestive heart failure ( J:304446 )

• homozygotes die shortly after birth due to heart failure

cellular

abnormal extracellular matrix morphology ( J:304446 )

• at E13.5, hearts show extracellular matrix (ECM) accumulation, as indicated by increased expression of Fn1 (fibronectin 1) and Lamb3 (laminin, beta 3)

muscle

abnormal trabecula carnea morphology ( J:304446 )

• at E13.5, trabeculae are morphologically distinct and not yet compacting

• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae

ventricle myocardium hypoplasia ( J:304446 )

• at P0, P5 and P7, ventricles show myocardial hypoplasia