Phenotypes associated with this allele

• Allele Symbol: Agt^tm1Afu
• Allele Name: targeted mutation 1, Akiyoshi Fukamizu
• Allele ID: MGI:2136636
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Agt^tm1Afu/Agt^tm1Afu	involves: C57BL/6 * CBA	MGI:3699327
hm2	Agt^tm1Afu/Agt^tm1Afu	involves: C57BL/6 * CBA * ICR	MGI:3609042
ht3	Agt^tm1Afu/Agt^+	involves: C57BL/6 * CBA * ICR	MGI:3609043
cx4	Agt^tm1Afu/Agt^tm1Afu Tg(Fabp4-Agt)1Mte/0	involves: C57BL/6 * CBA * DBA/2 * ICR	MGI:3609053
cx5	Agt^tm1Afu/Agt^tm1Afu Tg(Fabp4-Agt)2Mte/0	involves: C57BL/6 * CBA * DBA/2 * ICR	MGI:3609055

Genotype
MGI:3699327

hm1

• Allelic Composition: Agt^tm1Afu/Agt^tm1Afu
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:46506 )

• ~60% of homozygotes die during the third postnatal week

growth/size/body

decreased body weight ( J:46506 )

• at 10 weeks of age, homozygotes show a 10.4% decrease in body weight relative to wild-type controls

• after a 24-hr water deprivation period, homozygotes show a greater body weight loss (30%) than wild-type controls (25%)

slow postnatal weight gain ( J:46506 )

• homozygotes display a delayed weight gain after 9 weeks of age

increased kidney weight ( J:46506 )

• at 10 weeks of age, wet kidney weight relative to whole body weight is signifcantly increased relative to that in wild-type mice

• however, absolute kidney weight remains unchanged

renal/urinary system

decreased urine aldosterone level ( J:46506 )

• euhydrated homozygotes display a severe reduction in urinary excretion of aldosterone relative to wild-type controls

increased urine antidiuretic hormone level ( J:46506 )

• euhydrated homozygotes show a 2.9-fold increase in urinary excretion of vasopressin relative to wild-type controls

• after a 24-hr water deprivation period, homozygotes show a 5.5 increase in urinary excretion of vasopressin relative to wild-type controls

decreased urine potassium level ( J:46506 )

• euhydrated homozygotes display significantly lower urinary concentrations of potassium than wild-type controls

• during a 24-hr water deprivation period, homozygotes fail to increase their urinary potassium levels, unlike wild-type controls

decreased urine sodium level ( J:46506 )

• euhydrated homozygotes display significantly lower urinary concentrations of sodium than wild-type controls

• during a 24-hr water deprivation period, homozygotes fail to increase their urinary sodium levels, unlike wild-type controls

decreased urine osmolality ( J:46506 )

• euhydrated homozygotes display reduced urine osmolarity relative to wild-type controls

• during a 24-hr water deprivation period, homozygotes fail to significantly increase their urine osmolarity, unlike in wild-type controls where urine osmolality is increased by 72%

tubulointerstitial nephritis ( J:46506 )

• at 10 weeks of age, homozygotes display chronic interstitial inflammation

abnormal kidney morphology ( J:137944 )

• similar to that observed in Agtr1a^tm1Unc Agtr1b^tm1Cof double homozygotes or Agtr1a^tm1Unc Agtr1b^tm1Cof Agtr2^tm1Tin triple homozygotes

abnormal kidney afferent arteriole morphology ( J:46506 )

• at 10 weeks of age, wall thickening of the afferent arterioles is observed

abnormal kidney interlobular artery morphology ( J:46506 )

• at 10 weeks of age, wall thickening of the interlobular arteries is observed

increased kidney weight ( J:46506 )

• at 10 weeks of age, wet kidney weight relative to whole body weight is signifcantly increased relative to that in wild-type mice

• however, absolute kidney weight remains unchanged

decreased renal glomerulus number ( J:46506 )

• at 10 weeks of age, the mean glomerular count per maximal cross sectional area is signifcantly reduced

kidney papillary atrophy ( J:46506 )

• at 10 weeks of age, homozygotes display papillary atrophy

kidney medulla atrophy ( J:46506 )

• at 10 weeks of age, homozygotes display a thinned kidney medulla relative to wild-type controls

hydronephrosis ( J:46506 )

• at 10 weeks of age, homozygotes display a dilated renal pelvis

renal tubule atrophy ( J:46506 )

• at 10 weeks of age, homozygotes display atrophic renal tubules

decreased creatinine clearance ( J:46506 )

• after a 24-hr water deprivation period, homozygotes show a signifcant decrease in creatinine clearance, unlike wild-type controls

• however, euhydrated homozygotes display normal endogenous creatinine clearance and plasma creatinine levels

polyuria ( J:46506 )

• euhydrated homozygotes show increased urine output relative to wild-type controls

homeostasis/metabolism

increased circulating antidiuretic hormone level ( J:46506 )

• euhydrated homozygotes display significantly higher plasma vasoperssin levels (4.3x) than wild-type controls

decreased circulating aldosterone level ( J:46506 )

• euhydrated homozygotes show a 70% reduction in mean plasma aldosterone levels relative to wild-type controls

decreased urine aldosterone level ( J:46506 )

• euhydrated homozygotes display a severe reduction in urinary excretion of aldosterone relative to wild-type controls

increased urine antidiuretic hormone level ( J:46506 )

• euhydrated homozygotes show a 2.9-fold increase in urinary excretion of vasopressin relative to wild-type controls

• after a 24-hr water deprivation period, homozygotes show a 5.5 increase in urinary excretion of vasopressin relative to wild-type controls

decreased urine potassium level ( J:46506 )

• euhydrated homozygotes display significantly lower urinary concentrations of potassium than wild-type controls

• during a 24-hr water deprivation period, homozygotes fail to increase their urinary potassium levels, unlike wild-type controls

decreased urine sodium level ( J:46506 )

• euhydrated homozygotes display significantly lower urinary concentrations of sodium than wild-type controls

• during a 24-hr water deprivation period, homozygotes fail to increase their urinary sodium levels, unlike wild-type controls

decreased urine osmolality ( J:46506 )

• euhydrated homozygotes display reduced urine osmolarity relative to wild-type controls

• during a 24-hr water deprivation period, homozygotes fail to significantly increase their urine osmolarity, unlike in wild-type controls where urine osmolality is increased by 72%

cardiovascular system

abnormal kidney afferent arteriole morphology ( J:46506 )

• at 10 weeks of age, wall thickening of the afferent arterioles is observed

abnormal kidney interlobular artery morphology ( J:46506 )

• at 10 weeks of age, wall thickening of the interlobular arteries is observed

decreased systemic arterial systolic blood pressure ( J:46506 )

impaired blood-brain barrier function ( J:59299 )

• exhibit impaired blood-brain barrier function as indicated by leakage of Evans blue dye after cold injury

nervous system

impaired blood-brain barrier function ( J:59299 )

• exhibit impaired blood-brain barrier function as indicated by leakage of Evans blue dye after cold injury

abnormal hippocampus granule cell layer ( J:59299 )

• the granular layer cells of the hippocampus have larger nuclei and are round shaped with coarse chromatin and the cellular density is decreased with less layers

immune system

tubulointerstitial nephritis ( J:46506 )

• at 10 weeks of age, homozygotes display chronic interstitial inflammation

Genotype
MGI:3609042

hm2

• Allelic Composition: Agt^tm1Afu/Agt^tm1Afu
• Genetic Background: involves: C57BL/6 * CBA * ICR

cardiovascular system

abnormal kidney vasculature morphology ( J:36820 )

• vascular thickening in the kidneys that is evident at P7 and becomes prominent by 2 weeks after birth is composed of hyperplasia of vascular smooth muscle cells and juxtaglomerular apparatus cells

• vascular thickening is associated with distorted vascular integrity in conjunction with nonconcentric vascular thickening with luminal dilation

vascular smooth muscle hyperplasia ( J:36820 )

• limited to the kidneys

decreased systemic arterial blood pressure ( J:21887 )

• 20.8 mm Hg lower mean blood pressure

decreased systemic arterial diastolic blood pressure ( J:21887 )

• 14.3 mm Hg lower diastolic blood pressure

decreased systemic arterial systolic blood pressure ( J:21887 , J:73163 )

• 33.5 mm Hg lower systolic blood presure (J:21887)

hypotension ( J:21887 , J:36820 )

growth/size/body

decreased body size ( J:21887 )

• slight decrease in body size

decreased body weight ( J:73163 )

• exhibit lower body weight at weaning and lower fat-free mass

homeostasis/metabolism

abnormal blood homeostasis ( J:73163 )

decreased circulating angiotensinogen level ( J:21887 )

• undetectable levels of angiotensinogen and angiotensin I in the plasma

abnormal enzyme/coenzyme level ( J:38494 )

• overproduction of renal renin

increased circulating renin level ( J:36820 , J:73163 )

• higher plasma renin activity (J:73163)

muscle

vascular smooth muscle hyperplasia ( J:36820 )

• limited to the kidneys

renal/urinary system

abnormal kidney vasculature morphology ( J:36820 )

• vascular thickening in the kidneys that is evident at P7 and becomes prominent by 2 weeks after birth is composed of hyperplasia of vascular smooth muscle cells and juxtaglomerular apparatus cells

• vascular thickening is associated with distorted vascular integrity in conjunction with nonconcentric vascular thickening with luminal dilation

abnormal juxtaglomerular apparatus morphology ( J:36820 , J:73163 )

• hyperplasia of juxtaglomerular apparatus cells is seen at 2 weeks after birth (J:36820)

• hypertrophy and hyperplasia of the juxtaglomerular complexes (J:73163)

abnormal kidney inner medulla morphology ( J:73163 )

• inner medullary disorganization

kidney papillary atrophy ( J:36820 , J:73163 )

• atrophic papillae in newborns but not in embryos (J:36820)

hydronephrosis ( J:36820 )

• newborns, but not embryos, frequently exhibit dilation of the pelvis

polyuria ( J:36820 , J:73163 )

adipose tissue

decreased total body fat amount ( J:73163 )

• lower total fat mass, epididymal fat pad weight, and adiposity index than in wild-type

decreased fat cell size ( J:73163 )

• adipocyte cell diameter and weight are decreased compared to wild-type, indicating adipocyte hypotrophy

decreased epididymal fat pad weight ( J:73163 )

• lower epididymal fat pad weight

behavior/neurological

polydipsia ( J:73163 )

• increase in water consumption

increased locomotor activity ( J:73163 )

• locomotor activity, measured by total distance covered, is greater than in wild-type

Genotype
MGI:3609043

ht3

• Allelic Composition: Agt^tm1Afu/Agt⁺
• Genetic Background: involves: C57BL/6 * CBA * ICR

homeostasis/metabolism

abnormal blood homeostasis ( J:21887 )

• 58% decrease in angiotensinogen plasma levels and about 60% increase in angiotensin I plasma levels, however exhibit no blood pressure abnormalities

decreased circulating angiotensinogen level ( J:21887 )

• 58% decrease in angiotensinogen plasma levels

Genotype
MGI:3609053

cx4

• Allelic Composition: Agt^tm1Afu/Agt^tm1Afu; Tg(Fabp4-Agt)1Mte/0
• Genetic Background: involves: C57BL/6 * CBA * DBA/2 * ICR

cardiovascular system

hypertension ( J:73163 )

• slightly hypertensive compared to wild-type even though transgene expression rescues the decreased blood pressure phenotype observed in homozygous Agt mutant mice

Genotype
MGI:3609055

cx5

• Allelic Composition: Agt^tm1Afu/Agt^tm1Afu; Tg(Fabp4-Agt)2Mte/0
• Genetic Background: involves: C57BL/6 * CBA * DBA/2 * ICR

homeostasis/metabolism

decreased circulating angiotensinogen level ( J:73163 )

• plasma angiotensinogen levels are 20-30% of those in wild-type even though transgene expression rescues the Agt mutant phenotype and mutants are normotensive