Phenotypes associated with this allele

• Allele Symbol: Adm^tm1Hku
• Allele Name: targeted mutation 1, Hiroki Kurihara
• Allele ID: MGI:3043324
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adm^tm1Hku/Adm^tm1Hku	involves: 129S6/SvEvTac * C57BL/6	MGI:3043336
ht2	Adm^tm1Hku/Adm^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3043339

Genotype
MGI:3043336

hm1

• Allelic Composition: Adm^tm1Hku/Adm^tm1Hku
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:89608 )

• 83% of homozygotes die at E13.5, with none surviving to E14.5

• administration of recombinant adrenomedullin reduces the mortality rate at E13.5 to 21.4% and extends survival to E14.5

cardiovascular system

abnormal artery morphology ( J:89608 )

• numerous holes are observed on surfaces of corrosion casts of the aorta and cervical arteries

umbilical artery stenosis ( J:89608 )

• at E13.0, the umbilical artery is abnormally constricted

abnormal vascular endothelial cell morphology ( J:89608 )

• at E12.5, mutant endothelial cells are often detached from basement structure in vitelline vessels and in hepatic capillaries, allowing efflux of protoerythrocytes through disrupted barrier

• in addition, mutant endothelial cells are cuboid (instead of flat) and stand out from the wall of lumen in cervical arteries

abnormal liver vasculature morphology ( J:89608 )

• homozygotes display a complex mesh-like network of fused vessels in hepatic vasculature

umbilical vein stenosis ( J:89608 )

• at E13.0, the umbilical vein is abnormally constricted

abnormal vitelline vasculature morphology ( J:89608 )

• at E13.0, homozygotes exhibit poorly developed vitelline vessels in the yolk sac

pericardial effusion ( J:89608 )

• at E13.0, homozygotes show accumulation of pericardial effusion

hemorrhage ( J:89608 )

• at E13.5-E14.0, homozygotes display severe hemorrhage under the skin and in the lung and liver

• however, no hemorrhagic changes are apparent at E12.5 to E13.0

lung hemorrhage ( J:89608 )

• at E13.5-E14.0

liver hemorrhage ( J:89608 )

• at E13.5-E14.0

skin hemorrhage ( J:89608 )

• severe hemorrhage under the skin at E13.5-E14.0

embryo

umbilical artery stenosis ( J:89608 )

• at E13.0, the umbilical artery is abnormally constricted

umbilical vein stenosis ( J:89608 )

• at E13.0, the umbilical vein is abnormally constricted

abnormal vitelline vasculature morphology ( J:89608 )

• at E13.0, homozygotes exhibit poorly developed vitelline vessels in the yolk sac

abnormal placenta morphology ( J:89608 )

• at E13.0, the fetal side of the placenta appears ischemic

• sections of placenta show reduced numbers of embryonic protoerythrocytes in the capillaries, suggesting poor chorionic circulation

decreased placenta weight ( J:89608 )

• at E13.0, the weight of mutant placentas is significantly reduced relative to wild-type (0.057 0.005 g vs 0.0730.005 g, respectively)

homeostasis/metabolism

pericardial effusion ( J:89608 )

• at E13.0, homozygotes show accumulation of pericardial effusion

hydrops fetalis ( J:89608 )

• at E14.0, some homozygotes exhibit mild hydrops fetalis; however, many embryos display hemorrhage without severe edema

respiratory system

lung hemorrhage ( J:89608 )

• at E13.5-E14.0

integument

skin hemorrhage ( J:89608 )

• severe hemorrhage under the skin at E13.5-E14.0

liver/biliary system

abnormal liver vasculature morphology ( J:89608 )

• homozygotes display a complex mesh-like network of fused vessels in hepatic vasculature

liver hemorrhage ( J:89608 )

• at E13.5-E14.0

cellular

impaired basement membrane formation ( J:89608 )

• at E12.5, mutant embryos show absence of a detectable lamina densa as well as abnormal cytoplasmic projections of endothelial cells into the basement structure of major vessels

Genotype
MGI:3043339

ht2

• Allelic Composition: Adm^tm1Hku/Adm⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

cardiovascular system

cardiac hypertrophy ( J:106173 )

• heterozygotes show no significant differences in body size or heart and kidney weight relative to wild-type mice

• however, at 14 days after Ang II infusion, heterozygotes exhibit more severe cardiac hypertrophy than wild-type mice, as shown by a significantly higher increase in heart weight to body weight ratios

increased heart left ventricle wall thickness ( J:106173 )

• at 14 days after angiotensin II (Ang II) infusion, heterozygotes exhibit a significantly increased left ventricular wall thickness relative to wild-type mice (IVST; 1.16 0.09 mm vs 1.06 0.14 mm, respectively)

decreased heart ventricle muscle contractility ( J:106173 )

• heterozygotes exhibit a significantly lower ejection fraction both before and after Ang II infusion

increased systemic arterial blood pressure ( J:89608 )

• original findings indicate that adult heterozygotes show a mild (~10 mmHg) increase in arterial blood pressure relative to wild-type mice, associated with reduced nitric oxide production (J:89608)

• however, subsequent analysis showed no significant differences in systolic blood pressure changes induced by Ang II infusion (J:106173)

growth/size/body

cardiac hypertrophy ( J:106173 )

• heterozygotes show no significant differences in body size or heart and kidney weight relative to wild-type mice

• however, at 14 days after Ang II infusion, heterozygotes exhibit more severe cardiac hypertrophy than wild-type mice, as shown by a significantly higher increase in heart weight to body weight ratios

muscle

decreased heart ventricle muscle contractility ( J:106173 )

• heterozygotes exhibit a significantly lower ejection fraction both before and after Ang II infusion

renal/urinary system

glomerulosclerosis ( J:106173 )

• after Ang II infusion, heterozygotes display a more severe glomerulosclerosis and a higher glomerular injury score than wild-type mice

decreased creatinine clearance ( J:106173 )

• after Ang II infusion, heterozygotes display significantly reduced creatinine clearance relative to wild-type mice

oliguria ( J:106173 )

• heterozygotes exhibit a significantly reduced urine volume relative to wild-type mice

• after Ang II infusion, heterozygotes display a significantly lower increase in urine volume relative to wild-type mice

behavior/neurological

decreased fluid intake ( J:106173 )

• after Ang II infusion, heterozygotes exhibit a significantly lower water intake relative to wild-type mice