Phenotypes associated with this allele

• Allele Symbol: Hbegf^tm1Dcl
• Allele Name: targeted mutation 1, David C Lee
• Allele ID: MGI:2665039
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hbegf^tm1Dcl/Hbegf^tm1Dcl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3622104
cx2	Btc^tm1Dcl/Btc^tm1Dcl Hbegf^tm1Dcl/Hbegf^tm1Dcl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3622110

Genotype
MGI:3622104

hm1

• Allelic Composition: Hbegf^tm1Dcl/Hbegf^tm1Dcl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

premature death ( J:83820 )

• surviving homozygotes grow normally, are fertile and produce litters of normal size; however, 43% of adult male and female homozygotes die within 12 months

postnatal lethality ( J:83820 )

• only 40% of homozygotes survive to weaning

cardiovascular system

dilated aorta ( J:83820 )

• at 5 months, homozygotes display aortic dilation, a classic symptom of valvular stenosis

abnormal atrioventricular valve development ( J:83820 )

• mutant AV valves fail to undergo remodeling and form slender valve leaflets, and are only modestly reduced in size remaining 36-46% larger than wild-type counterparts through E15.5

• impaired remodeling of mutant AV valves is due to a ~3.5-fold increase in mesenchymal cell proliferation at E14.5 or later, and is associated with dramatic increases in activated Smad1/5/8

abnormal pulmonary valve development ( J:83820 )

• mutant PV valves fail to undergo remodeling and form slender valve leaflets, and are only modestly reduced in size remaining 36-46% larger than wild-type counterparts through E15.5

• impaired remodeling of mutant PV valves is due to a ~2-fold increase in mesenchymal cell proliferation at E14.5 or later, and is associated with dramatic increases in activated Smad1/5/8

atrioventricular valve stenosis ( J:83820 )

• all newborn homozygotes display stenotic atrioventricular valves

enlarged atrioventricular valve ( J:83820 )

• all newborn homozygotes display enlarged atrioventricular valves

enlarged heart ( J:83820 )

• at necropsy, homozygotes that die within the first year of life exhibit enlarged hearts and congested lungs, in the absence of other pathological defects

increased heart weight ( J:83820 )

• male homozygotes show a continuous increase in heart-to-body weight ratios from birth through 6 months of age, with the largest relative increase noted between 3 and 6 weeks

• at 6 weeks, the mean heart-to-body weight ratio for mutant mice is 1.27 +/- 0.20% vs 0.80 +/- 0.03% for wild-type mice

enlarged semilunar valve ( J:83820 )

• all newborn homozygotes display enlarged semilunar valves

enlarged aortic valve ( J:83820 )

• at birth, the mean area of mutant aortic valves is 56.7 +/- 17 mm² relative to 21.9 +/- 4.6 mm² in wild-type

enlarged pulmonary valve ( J:83820 )

semilunar valve stenosis ( J:83820 )

• all newborn homozygotes display stenotic semilunar valves

aortic valve stenosis ( J:83820 )

pulmonary valve stenosis ( J:83820 )

decreased ventricle muscle contractility ( J:83820 )

• at 5 months, male homozygotes exhibit reduced fractional shortening (51.6 +/- 7.4) relative to wild-type males (68.7 +/- 2.7), indicating significant systolic dysfunction

muscle

decreased ventricle muscle contractility ( J:83820 )

• at 5 months, male homozygotes exhibit reduced fractional shortening (51.6 +/- 7.4) relative to wild-type males (68.7 +/- 2.7), indicating significant systolic dysfunction

respiratory system

impaired lung alveolus development ( J:83820 )

• ~50% of mutant lungs exhibit significantly fewer alveoli than wild-type lungs (39.2 +/- 4.0 vs 28.1 +/- 6.7 per field)

pulmonary hypoplasia ( J:83820 )

• ~50% of newborn homozygotes exhibit hypoplastic, poorly differentiated lungs

abnormal pulmonary alveolus morphology ( J:83820 )

• ~50% of newborn homozygotes display thickened mesenchymal tissue between alveoli

abnormal type II pneumocyte morphology ( J:83820 )

• PAS staining indicates a high fraction of immature, glycogen-containing cells in newborn mutant lungs; conversely, fewer cells in mutant lungs stain positive for type II pneumocyte marker pro-surfactant C

skeleton

ectopic cartilage ( J:83820 )

• homozygotes display chondrocytes and ectopic cartilage formation throughout the aortic valve leaflets possibly as a result of disregulated BMP signaling in cardiac tissue

growth/size/body

enlarged heart ( J:83820 )

• at necropsy, homozygotes that die within the first year of life exhibit enlarged hearts and congested lungs, in the absence of other pathological defects

increased heart weight ( J:83820 )

• male homozygotes show a continuous increase in heart-to-body weight ratios from birth through 6 months of age, with the largest relative increase noted between 3 and 6 weeks

• at 6 weeks, the mean heart-to-body weight ratio for mutant mice is 1.27 +/- 0.20% vs 0.80 +/- 0.03% for wild-type mice

Genotype
MGI:3622110

cx2

• Allelic Composition: Btc^tm1Dcl/Btc^tm1Dcl; Hbegf^tm1Dcl/Hbegf^tm1Dcl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:83820 )

• 54% of double homozygotes die by 4 months of age while 83% are found dead within the first year, indicating a further reduction in lifespan relative to single Hbegf^tm1Dcl homozygotes

cardiovascular system

enlarged atrioventricular valve ( J:83820 )

• newborn double homozygotes display enlarged atrioventricular valves

dilated heart left atrium ( J:83820 )

• adult double homozygotes exhibit left atrial dilation, rarely or never observed in single Hbegf^tm1Dcl homozygotes

enlarged semilunar valve ( J:83820 )

• newborn double homozygotes display enlarged semilunar valves

enlarged aortic valve ( J:83820 )

• newborn double homozygotes display enlarged aortic valves; however, the mean aortic valve area of double mutants is not significantly different from that of single Hbegf^tm1Dcl homozygotes

enlarged pulmonary valve ( J:83820 )

cardiac fibrosis ( J:83820 )

• at ~2 months, moribund double homozygotes exhibit extensive intraventricular or focal epicardial fibrosis within or on the left ventricle, rarely or never observed in single Hbegf^tm1Dcl homozygotes

decreased ventricle muscle contractility ( J:83820 )

• at 4 months, male double homozygotes exhibit reduced fractional shortening (58.8 +/- 15.9) relative to wild-type males (71.8 +/- 3.3), indicating significant systolic dysfunction

muscle

decreased ventricle muscle contractility ( J:83820 )

• at 4 months, male double homozygotes exhibit reduced fractional shortening (58.8 +/- 15.9) relative to wild-type males (71.8 +/- 3.3), indicating significant systolic dysfunction

homeostasis/metabolism

abnormal atrial thrombosis ( J:83820 )

• adult double homozygotes exhibit left atrial thrombosis, rarely or never observed in single Hbegf^tm1Dcl homozygotes

growth/size/body

decreased body weight ( J:83820 )

• at 4 months, male double homozygotes exhibit a reduced body weight (29.0 +/- 2.5) relative to wild-type males (33.6 +/- 2.8 g)

skeleton

ectopic cartilage ( J:83820 )

• double homozygotes display chondrocytes and ectopic cartilage formation throughout the aortic valve leaflets, similar to single Hbegf^tm1Dcl homozygotes