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 )

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

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

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support.	last database update 12/10/2024 MGI 6.24