Phenotypes associated with this allele

• Allele Symbol: Agtr1a^tm1Tma
• Allele Name: targeted mutation 1, Taiji Matsusaka
• Allele ID: MGI:2183541
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Agtr1a^tm1Tma/Agtr1a^tm1Tma	involves: 129P2/OlaHsd * C57BL/6	MGI:3656060
cx2	Agtr1a^tm1Tma/Agtr1a^tm1Tma Agtr1b^tm1Ii/Agtr1b^tm1Ii	involves: 129P2/OlaHsd * C57BL/6	MGI:3656059

Genotype
MGI:3656060

hm1

• Allelic Composition: Agtr1a^tm1Tma/Agtr1a^tm1Tma
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

renal/urinary system

abnormal kidney interlobular artery morphology ( J:36090 )

• interlobular artery is abnormally hypertrophic compared to wild-type

abnormal juxtaglomerular apparatus morphology ( J:36090 )

• markedly enlarged compared to wild-type

juxtaglomerular cell hyperplasia ( J:36090 )

• there are increased numbers of renin-secreting cells compared to wild-type

cardiovascular system

abnormal kidney interlobular artery morphology ( J:36090 )

• interlobular artery is abnormally hypertrophic compared to wild-type

increased systemic arterial blood pressure ( J:46007 )

• mice show a dose-dependent increase in blood pressure but change from baseline is significantly less than that observed in wild-type

Genotype
MGI:3656059

cx2

• Allelic Composition: Agtr1a^tm1Tma/Agtr1a^tm1Tma; Agtr1b^tm1Ii/Agtr1b^tm1Ii
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:46007 )

• a high proportion of double-null animals die prior to weaning

• at weaning there is a highly significant deviation of observed double homozygotes vs expected; 26 double-null pups are expected but only 7 are observed; numbers of eac genotype conform to expected ratios

renal/urinary system

abnormal kidney vasculature morphology ( J:46007 , J:112003 )

• mice have renal arterial lesions such as prominent medial hyperplasia of the interlobular arteries and afferent arterioles (J:46007)

• at 3 weeks of age, mice demonstrate a significant increase in wall thickness vs wild-type and Agt-null mice and wall thickness ratio vs wild-type (J:46007)

• mutants show vascular thickening compared to wild-type as measured by vascular wall thickness ratios noticeable at 1 week in renal arterioles and becoming prominent by 2 weeks (wild-type vs double-null: 0.51 vs 0.57 at 1 week, 0.51 vs 0.61 at 2 weeks and 0.55 vs 0.65 at 3 weeks) (J:112003)

• blockade of kallikrein and bradykinin B2 receptors from 3 to 14 days accelerates vascular hypertrophy in double mutants while there is not effect in wild-type (J:112003)

abnormal kidney development ( J:46007 )

• at 1 week of age, mice show a delay in glomerular maturity (maturity index of 1.84 in wild-type at 3 weeks of age vs 1.40 in double-nulls)

abnormal kidney papilla morphology ( J:46007 )

• kidneys show progressive changes in the papilla similar to Agtr1a-null mice

kidney papillary hypoplasia ( J:46007 )

• mice have hypoplastic papilla (0.86 mm in wild-type vs 0.30 mm in mutants at 9 weeks of age)

dilated kidney calyx ( J:46007 )

• kidneys show progressive changes in the calyx similar to Agtr1a-null mice

• double-null animals show a widening calyx space (calyx-to-papilla diameter ratio; ratio is 1.57 in wild-type vs 1.75 in double nulls at birth to 1.38 vs 5.65 in double nulls at 9 weeks of age

absent kidney pelvis ( J:112003 )

• in all double mutants, kidneys lack the renal pelvis

cardiovascular system

abnormal kidney vasculature morphology ( J:46007 , J:112003 )

• mice have renal arterial lesions such as prominent medial hyperplasia of the interlobular arteries and afferent arterioles (J:46007)

• at 3 weeks of age, mice demonstrate a significant increase in wall thickness vs wild-type and Agt-null mice and wall thickness ratio vs wild-type (J:46007)

• mutants show vascular thickening compared to wild-type as measured by vascular wall thickness ratios noticeable at 1 week in renal arterioles and becoming prominent by 2 weeks (wild-type vs double-null: 0.51 vs 0.57 at 1 week, 0.51 vs 0.61 at 2 weeks and 0.55 vs 0.65 at 3 weeks) (J:112003)

• blockade of kallikrein and bradykinin B2 receptors from 3 to 14 days accelerates vascular hypertrophy in double mutants while there is not effect in wild-type (J:112003)

ventricular septal defect ( J:46007 )

• 2 double-null mice that died before weaning were found to have large ventricular septal defects involving both membranous and muscular portions; none were seen in any other genotype

perimembraneous ventricular septal defect ( J:46007 )

• seen in 2 double-null mice that died before weaning

muscular ventricular septal defect ( J:46007 )

• seen in 2 double-null mice that died before weaning

decreased heart weight ( J:46007 )

• double-nulls have the lowest heart weights of any genotype but difference compared to wild-type does not reach statistical significance

abnormal systemic arterial blood pressure ( J:46007 )

• infusion of angiotensin II cause no change in blood pressure from basline

decreased systemic arterial blood pressure ( J:46007 )

• in conscious animals, blood pressure averages 72 mm Hg vs 106 mm Hg in wild-type

• under anesthesia, baseline MAP is 42 mm Hg vs 96 mm Hg in wild-type controls