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Phenotypes Associated with This Genotype
Genotype
MGI:4366437
Allelic
Composition
Nos3tm1Plh/Nos3tm1Plh
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nos3tm1Plh mutation (1 available); any Nos3 mutation (58 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• increase in mortality 24 h after infection with S. pneumoniae strain type 3

immune system
• S. pneumoniae strain type 3 induced increases in intracranial pressure and cerebral spinal fluid leukocyte counts and impairment of the brain blood barrier are enhanced
• display more pronounced subarachnoid and ventricular granulocytic infiltrates 24 h after infection with S. pneumoniae strain type 3
• increase in mortality 24 h after infection with S. pneumoniae strain type 3

cardiovascular system
• mice raised in mild hypoxia display a decreased vessel volume density compared to similarly raised wild-type controls
• left ventricular chamber size is reduced
• sarcomere shortening in response to a beta3-adrenergic agonist is absent
• increase in the beta-adrenergic inotropic responses
• Ca2+ transients in response to a beta3-adrenergic agonist are absent
• in male, but not female, mice (J:108540)
• arterial elastance is increased (J:75645)
• relaxation of mesenteric arteries and the aorta of acetylcholine-treat male mice is inhibited unlike similarly treated female and wild-type mice (J:108540)
• following exposure to 75% oxygen from P7 to P12, extraretinal neovascularization upon return to room air is significantly decreased compared to similarly treated wild-type mice
• neointimal formation after cuff injury is increased compared to wild-type controls (J:119617)
• neointimal formation after cuff injury is increased in males relative to females (J:119617)
• neointimal formation after cuff injury is decreased in pregnant females compared to non pregnant females; however, the level in mutants is still increased compared to wild-type (J:119617)
• at day 28 following femoral artery resection limb perfusion remains impaired unlike in wild-type mice (J:139343)
• capillary density remains reduced for a longer period of time following femoral artery resection (J:139343)
• VEGF treatment fails to improve angiogenesis following femoral artery resection (J:139343)

homeostasis/metabolism
N
• despite increase in visceral fat, no change in triacylglycerol levels in the blood are detected
• neointimal formation after cuff injury is increased compared to wild-type controls (J:119617)
• neointimal formation after cuff injury is increased in males relative to females (J:119617)
• neointimal formation after cuff injury is decreased in pregnant females compared to non pregnant females; however, the level in mutants is still increased compared to wild-type (J:119617)
• at day 28 following femoral artery resection limb perfusion remains impaired unlike in wild-type mice (J:139343)
• capillary density remains reduced for a longer period of time following femoral artery resection (J:139343)
• VEGF treatment fails to improve angiogenesis following femoral artery resection (J:139343)
• following superovulation the plasma estradiol level is significantly higher in homozygous mutant females compared to wild-type mice
• relaxation of mesenteric arteries and the aorta of acetylcholine-treat male mice is inhibited unlike similarly treated female and wild-type mice

reproductive system
• oocytes with an unusually large first polar body are observed
• a variety of abnormal characteristics noted including enlarged first polar body, cytoplasmic cleavage, blebbing, premature release of the second polar body and cell division
• fewer oocytes from mutant females reach metaphase II of meiosis but instead remain in metaphase I or become abnormal with an enlarged first polar body, cytoplasmic cleavage, blebbing, and/or premature release of the second polar body
• many of the arrested and abnormal oocytes are also dying
• ovaries from homozygous mutant females are significantly smaller than those from wild-type females following stimulation by exogenous gonadotropins
• the number of ovarian rupture sites stimulated by exogenous gonadotropins is decreased in mutant females compared to wild-type mice
• the number of oocytes released following stimulation by exogenous gonadotropins is decreased in mutant females compared to wild-type mice
• mutants produced 62% fewer oocytes than controls after superovualtion
• oestrus cycle length and individual variability in cycle length is reduced in homozygous mutant females compared to C57BL/6J wild-type mice
• homozygous mutant females have a smaller average litter size compared to wild-type mice (J:58361)
• a lower percentage of pups are weaned by homozygous mutant females compared to wild-type mice (J:58361)
• matings between homozygous mutants produce smaller litters size compared to matings between wild-type mice or heterozygous mice (J:89702)
• a lower percentage of pups born to homozygous mutant females survive to weaning (J:89702)
• litters from homozygous mutant females have a decreased ratio of female to male pups (J:89702)

endocrine/exocrine glands
• ovaries from homozygous mutant females are significantly smaller than those from wild-type females following stimulation by exogenous gonadotropins

muscle
• sarcomere shortening in response to a beta3-adrenergic agonist is absent
• increase in the beta-adrenergic inotropic responses

vision/eye
• following exposure to 75% oxygen from P7 to P12, extraretinal neovascularization upon return to room air is significantly decreased compared to similarly treated wild-type mice
• decrease capillary loss following exposure to 75% oxygen from P7 to P9 compared to similarly treated wild-type mice
• levels of nitrotyrosine in mutants exposed to hyperoxic conditions are not significantly increased compared to room air controls, unlike in wild-type mice

limbs/digits/tail
• bone volume is decreased at 6 and 9 weeks of age
• mean trabecular thickness, osteoid surface, osteoblast surface, mineralizing surface, and eroded surface are reduced at 6 weeks of age
• detected at 6, 9 and 18 weeks of age

renal/urinary system
• mild glomerular hypercellularity is seen in about 10% of mice at 9 weeks of age

skeleton
• after 5 days in culture the number of osteoblasts is significantly reduced compared to wild-type cells
• in culture osteoblasts have decreased alkaline phosphatase activity and form fewer mineralized nodules compared to wild-type cells
• stimulation with 17-beta-estradiol fails to stimulate osteoblast proliferation in culture
• cytokine (TGFB) stimulated migration is attenuated in culture osteoblasts compared to wild-type cells
• bone volume is decreased at 6 and 9 weeks of age
• mean trabecular thickness, osteoid surface, osteoblast surface, mineralizing surface, and eroded surface are reduced at 6 weeks of age
• detected at 6, 9 and 18 weeks of age
• in the femur, osteoid surface, mineralizing surface, and osteoblast surface are reduced at 6 weeks of age
• at 8 weeks of age, femoral/pelvic, spinal, and whole body total bone mineral density are reduced
• however, at 12 weeks of age no significant difference in bone mineral density is detected
• mean trabecular thickness in the femur is reduced at 6 and 18 weeks of age
• at 6 weeks of age the mineral apposition rate is modestly decreased in the femur

growth/size/body
• at P11 mice raised in 16% oxygen (mild hypoxia) weigh less than similarly raised wild-type controls
• at 1 year of age

respiratory system
• mice raised in mild hypoxia display a decreased vessel volume density compared to similarly raised wild-type controls
• mice raised in mild hypoxia display an increased mean lung intercept indicating an increase in intra-alveolar distance and a decreased radial alveolar count compared to similarly raised wild-type controls

behavior/neurological
• less helpless (reduced escape latency, fewer failures, and improved avoidance of the aversive stimulus) in a learned helplessness paradigm
• differences are not the result of differences in pain sensitivity, activity level, or anxiety level

nervous system
• significant decrease in progenitor cell proliferation
• the granule cell layer is increased in volume
• decrease in the percentage of pyknotic cells in the brain; however, the number of degenerating cells (detected by Fluoro-Jade B staining) is increased

adipose tissue
• increase in the amount of visceral fat at 1 year of age

liver/biliary system
• increased accumulation of glycogen is seen predominantly in zone 1 of the liver
• hepatocytes in zone one (closest to the artery) contain fewer mitochondria, while hepatocytes in zone 3 contain more mitochondria compared to wild-type cells from the same zone
• massive fat deposition is seen in zone 3 of the liver
• the ratio of cytosolic citrate synthase activity to NADH-cytochrome c oxidoreductase (KI+III) activity is elevated in liver homogenates

cellular
• oocytes with an unusually large first polar body are observed
• a variety of abnormal characteristics noted including enlarged first polar body, cytoplasmic cleavage, blebbing, premature release of the second polar body and cell division
• fewer oocytes from mutant females reach metaphase II of meiosis but instead remain in metaphase I or become abnormal with an enlarged first polar body, cytoplasmic cleavage, blebbing, and/or premature release of the second polar body
• many of the arrested and abnormal oocytes are also dying
• significant decrease in progenitor cell proliferation
• after 5 days in culture the number of osteoblasts is significantly reduced compared to wild-type cells
• in culture osteoblasts have decreased alkaline phosphatase activity and form fewer mineralized nodules compared to wild-type cells
• stimulation with 17-beta-estradiol fails to stimulate osteoblast proliferation in culture
• cytokine (TGFB) stimulated migration is attenuated in culture osteoblasts compared to wild-type cells
• 42% of pups born to homozygous females are dead by weaning


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/25/2025
MGI 6.24
The Jackson Laboratory