Phenotypes associated with this allele

• Allele Symbol: Hbegf^tm1.1Mek
• Allele Name: targeted mutation 1.1, Eisuke Mekada
• Allele ID: MGI:2655703
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hbegf^tm1.1Mek/Hbegf^tm1.1Mek	B6.Cg-Hbegf^tm1.1Mek	MGI:4818456
hm2	Hbegf^tm1.1Mek/Hbegf^tm1.1Mek	involves: C57BL/6 * C57BL/6J * CBA	MGI:3785447
ht3	Hbegf^tm1.1Mek/Hbegf^+	B6.Cg-Hbegf^tm1.1Mek	MGI:4818457
ht4	Hbegf^tm1.1Mek/Hbegf^+	involves: C57BL/6 * C57BL/6J * CBA	MGI:3785448

Genotype
MGI:4818456

hm1

• Allelic Composition: Hbegf^tm1.1Mek/Hbegf^tm1.1Mek
• Genetic Background: B6.Cg-Hbegf^tm1.1Mek

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

cardiovascular system

abnormal atrioventricular valve morphology ( J:161948 )

• atrioventricular valve thickness is increased compared to in wild-type mice

abnormal heart ventricle outflow tract morphology ( J:161948 )

• outflow tract valve thickness is increased compared to in wild-type mice

abnormal cardiovascular system physiology ( J:161948 )

• mesenchyme cells from cushion explants exhibit increased proliferation compared with similarly treated wild-type explants

• proliferation of outflow tract (OFT) and atrioventricular (AV) valve mesenchyme in culture is increased compared to in wild-type mice

• however, in vivo proliferation of endocardium, proliferation of endocardial cell from cushion explants, and apoptosis of OFT and AV endocardium and mesenchyme are normal

Genotype
MGI:3785447

hm2

• Allelic Composition: Hbegf^tm1.1Mek/Hbegf^tm1.1Mek
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA

mortality/aging

premature death ( J:82728 )

• more than 50% of homozygotes that survive the first postnatal week die at P25

postnatal lethality, incomplete penetrance ( J:82728 )

• over 60% of homozygotes die within the first week of life

cardiovascular system

increased myocardial fiber size ( J:82728 )

• at 12 weeks, the size of mutant cardiomyocytes is enlarged by ~2-fold relative to that in control mice, indicating myofiber hypertrophy

• however, no cardiomyocyte hypertrophy is noted at E19.5

abnormal atrioventricular valve morphology ( J:82728 )

• at E19.5, mutant hearts exhibit enlarged atrioventricular valves with an abnormal thickened globular morphology relative to control hearts

• however, no fibrosis is observed, suggesting that valve thickening is due to an increased number of mesenchymal cells

thick mitral valve ( J:82728 )

• mutant mitral valves appear thickened both at E19.5 and at 12 weeks of age

• at 12 weeks, the rate of thickening of the mitral valve is relatively lower than that of the aortic valve

thick tricuspid valve ( J:82728 )

• at E19.5, mutant tricuspid valves appear thickened relative to control valves

enlarged atrioventricular valve ( J:82728 )

• at E19.5

enlarged mitral valve ( J:82728 )

• mutant mitral valves appear enlarged and thickened both at E19.5 and at 12 weeks of age

enlarged tricuspid valve ( J:82728 )

• at E19.5, mutant tricuspid valves appear enlarged relative to control valves

enlarged heart ( J:82728 )

• at 6 weeks of age, homozygotes display massively enlarged hearts

• heart enlargement is evident as early as E19.5

abnormal semilunar valve morphology ( J:82728 )

• at E19.5, mutant hearts exhibit enlarged semilunar valves with an abnormal thickened globular morphology relative to control hearts

• however, no fibrosis is observed, suggesting that valve thickening is due to an increased number of mesenchymal cells

thick aortic valve ( J:82728 )

• mutant aortic valves appear thickened both at E19.5 and at 12 weeks of age

thick pulmonary valve ( J:82728 )

• at E19.5, mutant pulmonary valves appear thickened relative to control valves

enlarged semilunar valve ( J:82728 )

• at E19.5

enlarged aortic valve ( J:82728 )

• mutant aortic valves appear enlarged and thickened both at E19.5 and at 12 weeks of age

enlarged pulmonary valve ( J:82728 )

• at E19.5, mutant pulmonary valves appear enlarged relative to control valves

dilated heart ventricle ( J:82728 )

• at E19.5, both left (LV) and right (RV) ventricular chambers are dilated relative to those in control hearts

• at 12 weeks of age, homozygotes show progressive dilation of both ventricular chambers relative to controls

dilated heart left ventricle ( J:82728 )

• at 8-12 weeks, transthoracic echocardiography indicates marked dilation of the LV diameter, with an average LV end-diastolic value of 4.53 mm vs 2.87 mm in control mice

dilated heart right ventricle ( J:82728 )

decreased heart ventricle muscle contractility ( J:82728 )

• at 8-12 weeks, the ventricular fractional shortening (FS) is reduced to 29% in mutant mice relative to 49% in control mice

• however, no differences in body weight, heart rate, and systolic or diastolic blood pressures are observed relative to control mice

muscle

increased myocardial fiber size ( J:82728 )

• at 12 weeks, the size of mutant cardiomyocytes is enlarged by ~2-fold relative to that in control mice, indicating myofiber hypertrophy

• however, no cardiomyocyte hypertrophy is noted at E19.5

decreased heart ventricle muscle contractility ( J:82728 )

• at 8-12 weeks, the ventricular fractional shortening (FS) is reduced to 29% in mutant mice relative to 49% in control mice

• however, no differences in body weight, heart rate, and systolic or diastolic blood pressures are observed relative to control mice

growth/size/body

enlarged heart ( J:82728 )

• at 6 weeks of age, homozygotes display massively enlarged hearts

• heart enlargement is evident as early as E19.5

Genotype
MGI:4818457

ht3

• Allelic Composition: Hbegf^tm1.1Mek/Hbegf⁺
• Genetic Background: B6.Cg-Hbegf^tm1.1Mek

cardiovascular system

abnormal cardiovascular system physiology ( J:161948 )

• mesenchyme cells from cushion explants exhibit increased proliferation compared with similarly treated wild-type explants

• however, proliferation of endocardial cells from cushion explants is normal

Genotype
MGI:3785448

ht4

• Allelic Composition: Hbegf^tm1.1Mek/Hbegf⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA

normal phenotype

no abnormal phenotype detected ( J:82728 )

• heterozygotes display no overt abnormalities