All Phenotypes Npr1<tm1Mae> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Npr1^tm1Mae/Npr1^tm1Mae	B6.129P2-Npr1^tm1Mae	MGI:3665579
hm2	Npr1^tm1Mae/Npr1^tm1Mae	involves: 129P2/OlaHsd * C57BL/6	MGI:3619919
ht3	Npr1^tm1Mae/Npr1⁺	B6.129P2-Npr1^tm1Mae	MGI:3686525
ht4	Npr1^tm1Mae/Npr1⁺	involves: 129P2/OlaHsd * C57BL/6	MGI:3664252

Allelic Composition	Npr1^tm1Mae/Npr1^tm1Mae
Genetic Background	B6.129P2-Npr1^tm1Mae

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npr1^tm1Mae mutation (0 available); any Npr1 mutation (60 available)

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

mortality/aging

mortality/aging ( J:101857 )

N	• Background Sensitivity: sudden death occuring in F2 generation males of a mixed genetic background is no longer present in homozygotes after 6 or 7 backcrosses to C57BL/6, possibly due to genetic drifts and loss of modifying loci

cardiovascular system

enlarged heart ( J:78579 )

• adult homozygotes have significantly larger hearts than wild-type mice, as shown by increased HW/BW ratios

cardiac hypertrophy ( J:78579 , J:101857 )

• adult homozygotes exhibit cardiac hypertrophy versus wild-type mice at baseline (J:78579)

• in response to volume overlaod, homozygotes with aortocaval fistula display a change in LV geometry from concentric cardiac hypertrophy to borderline of concentric and eccentric hypertrophy (J:101857)

• in contrast, wild-type with aortocaval fistula exhibit a change in LV geometry from a normal pattern to eccentric hypertrophy (J:101857)

hypertension ( J:78579 )

• adult homozygotes (4-12 months) have significantly higher blood pressure levels than wild-type control mice (126 3 mmHg vs 108 2 mmHg, respectively)

• however, no significant difference in blood pressures between male and female homozygotes is observed

congestive heart failure ( J:101857 )

• in response to volume overlaod, homozygotes with aortocaval fistula exhibit increased susceptibility to heart failure, as shown by higher LV end-diastolic pressure, LV and RV weights, atrial weights, lung weight, and LV dimension, as well as lower fractional shortening and urinary sodium and cyclic guanosine monophosphate (cGMP) excretion than wild-type mice with aortocaval fistula

• ventricular mRNA expression of natriuretic peptides and beta-myosin heavy chain increases significantly only in mutant mice with aortocaval fistula

• plasma ANP, renin, and aldosterone, but not cGMP, exhibit greater responses to aortocaval fistula in homozygous mutant mice

• both sham-operated and aortocaval fistula heterozygous mice almost consistently display a phenotype intermediate between those of homozygous and wild-type mice

homeostasis/metabolism

increased circulating atrial natriuretic factor ( J:78579 )

• adult male (but not female) homozygotes display significantly higher circulating ANP levels relative to sex-matched wild-type counterparts

• in contrast to wild-type mice, male homozygotes have significantly greater levels of plasma ANP than female homozygotes

• however, a greater increase in ventricular ANP and BNP gene expression and ANP immunoreactivity is noted in female vs male homozygotes; increased expression is highly correlated to the degree of cardiac hypertrophy and is localized to the LV inner free wall and to areas of ventricular fibrosis

growth/size/body

enlarged heart ( J:78579 )

• adult homozygotes have significantly larger hearts than wild-type mice, as shown by increased HW/BW ratios

cardiac hypertrophy ( J:78579 , J:101857 )

• adult homozygotes exhibit cardiac hypertrophy versus wild-type mice at baseline (J:78579)

• in contrast, wild-type with aortocaval fistula exhibit a change in LV geometry from a normal pattern to eccentric hypertrophy (J:101857)

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

Cardiac hypertrophy in Npr1^tm1Mae/Npr1^tm1Mae male mice

mortality/aging

premature death ( J:74420 , J:101857 )

• at weaning, homozygotes are represented in normal Mendelian ratios; however, all (15 of 15) male but only 1 of 16 female homozygotes exhibit sudden death before 6 months of age (J:74420)

• notably, 7 of 7 male homozygotes die between 7 and 8 weeks when housed with littermates; when housed alone, all male homozygotes die beginning at ~9 weeks (J:74420)

• sudden death may be precipitated by stress (e.g. after prolonged voluntary exercise, placement with other males, or high-salt intake) (J:74420)

• Background Sensitivity: sudden death occuring in F2 generation males is no longer present in homozygotes after 6 or 7 backcrosses to C57BL/6, possibly due to genetic drifts and loss of modifying loci (J:101857)

cellular

cardiac interstitial fibrosis ( J:74420 )

• at 3-5 months, all (4 of 4) male homozygotes display perivascular fibrosis with variable scarring

• in contrast, only 1 of 5 female homozygotes display fibrotic foci at 6 months

cardiovascular system

aortic dissection ( J:74420 )

• at necropsy, 3 of 8 male homozygotes display aortic dissections

abnormal myocardium layer morphology ( J:74420 )

• at 3 to 5 months, male homozygotes with a hypertrophic myocardium show a >200% increase in myocyte cross-sectional area relative to wild-type mice

myocardium necrosis ( J:74420 )

• at 3-5 months, some male homozygotes exhibit patchy areas of incipient myocyte death in the ventricles

cardiac hypertrophy ( J:74420 )

• by 3 months of age, male and female homozygotes display an increased heart-to-body weight ratio averaging 185% and 133% of wild-type males and females, respectively

• by 4-5 months, homozygotes of both sexes show heart-to-body weight ratios averaging >160% of wild-type, with significantly increased left auricle-to-body weight ratios (250%), right auricle (220%), right ventricle (160%), and left ventricle (150%)

dilated heart left ventricle ( J:74420 )

• by 4-5 months, all homozygotes of both sexes show dilated ventricles, with a mean of >125% wild-type left ventricular end diastolic dimension and end systolic dimensions

• however, left ventricular performance remains intact and no evidence of myocardial dysfunction is observed

dilated heart right ventricle ( J:74420 )

• by 4-5 months, all homozygotes of both sexes display right ventricle-to-body weight ratios averaging >160% of wild-type

cardiac interstitial fibrosis ( J:74420 )

• at 3-5 months, all (4 of 4) male homozygotes display perivascular fibrosis with variable scarring

• in contrast, only 1 of 5 female homozygotes display fibrotic foci at 6 months

abnormal pulmonary circulation ( J:74420 )

• at necropsy, 4 of 8 male homozygotes display congested lungs

pulmonary embolism ( J:74420 )

• 1 of 8 male homozygotes died with external bleeding of unknown origin, also displaying a pulmonary artery luminal inclusion resulting from pulmonary embolism

salt-resistant hypertension ( J:74420 )

• on a low (0.05% NaCl), intermediate (2% NaCl), or high (8% NaCl) salt diet, young adult male and female homozygotes exhibit an average increase in blood pressure of 16 mmHg relative to sex-matched wild-type littermates

• on all three diets, both wild-type and homozygous mutant males display significantly higher blood pressures relative to genotype-matched females (average difference 10 mmHg)

• however, no significant effects of diet on the blood pressures of either sex and of either genotype are detected

congestive heart failure ( J:74420 )

• at necropsy, 4 of 8 male homozygotes display congested hearts

growth/size/body

cardiac hypertrophy ( J:74420 )

• by 3 months of age, male and female homozygotes display an increased heart-to-body weight ratio averaging 185% and 133% of wild-type males and females, respectively

homeostasis/metabolism

decreased circulating testosterone level ( J:58344 )

• serum testosterone level is 62% lower than in controls

decreased circulating renin level ( J:74420 )

• homozygotes exhibit less than one-third of plasma renin concentration relative to wild-type mice

muscle

abnormal myocardium layer morphology ( J:74420 )

• at 3 to 5 months, male homozygotes with a hypertrophic myocardium show a >200% increase in myocyte cross-sectional area relative to wild-type mice

myocardium necrosis ( J:74420 )

• at 3-5 months, some male homozygotes exhibit patchy areas of incipient myocyte death in the ventricles

respiratory system

abnormal pulmonary circulation ( J:74420 )

• at necropsy, 4 of 8 male homozygotes display congested lungs

pulmonary embolism ( J:74420 )

• 1 of 8 male homozygotes died with external bleeding of unknown origin, also displaying a pulmonary artery luminal inclusion resulting from pulmonary embolism

endocrine/exocrine glands

abnormal sex gland physiology ( J:58344 )

• Leydig cells do not show atrial natriuretic peptide (ANP)-stimulated guanylyl cyclase activation or cGMP accumulation and have no ANP-dependent testosterone production

reproductive system

abnormal sex gland physiology ( J:58344 )

• Leydig cells do not show atrial natriuretic peptide (ANP)-stimulated guanylyl cyclase activation or cGMP accumulation and have no ANP-dependent testosterone production

Allelic Composition	Npr1^tm1Mae/Npr1⁺
Genetic Background	B6.129P2-Npr1^tm1Mae

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npr1^tm1Mae mutation (0 available); any Npr1 mutation (60 available)

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

cardiovascular system

congestive heart failure ( J:101857 )

• in response to volume overlaod, both sham-operated and aortocaval fistula heterozygotes exhibit a susceptibility to heart failure that is intermediate between that of homozygous mutant and wild-type mice

Allelic Composition	Npr1^tm1Mae/Npr1⁺
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npr1^tm1Mae mutation (0 available); any Npr1 mutation (60 available)

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

cardiovascular system

increased systemic arterial blood pressure ( J:46175 )

• males exhibit blood pressures an average of 9.1 mmHg above wild-type

• show a significant increase in blood pressure as dietary salt is increased

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