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Phenotypes Associated with This Genotype
Genotype
MGI:2174975
Allelic
Composition
Nos1tm1Plh/Nos1tm1Plh
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nos1tm1Plh mutation (3 available); any Nos1 mutation (50 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• in anesthetized mice under 12% oxygen all mutant mice survived while 4 of 14 wild-type mice died
• survival at 20 months is reduced compared to Nos3 null mice
• slight increase in premature death (J:16390)
• survival at 20 months is reduced compared to Nos3 null mice (J:129064)
• the relative risk of death by 20 months of age is 2.5 times higher than in Nos3 null mice (J:129064)

digestive/alimentary system
• hypertrophy of the pyloric sphincter and the circular muscle layer
• with age, the stomachs lose their interior folds and undergo thinning of the walls, however the intestine appears normal
• stomach dilation, however architecture of the stomach layers is preserved

reproductive system
• ovulatory efficiency (number oocytes recovered divided by the number of ovarian rupture sites) is reduced in homozygotes
• significantly fewer oocytes are recovered following gonadotropin-stimulated ovulation in homozygous mutant females compared to wild-type females

nervous system
N
• homozygous mice do not exhibit defects in brain structure or neuron degeneration
• delay in Wallerian degeneration following transection of the sciatic nerve in the right hindlimb
• electron microscopy analysis indicates a lower density of mitochondria in the cortex of the brain
• however, the ratio of mitochondrial to nuclear DNA is similar to controls
• motor neurons display a significant decrease in the number of dendritic branches
• however, the number of primary dendrites, the longest dendritic path from a cell, and cell body size are not different from wild-type controls
• motor neurons display a significant decrease in the number of dendritic branches
• decrease in the number of branches is first detected at about 100 um from the cell body with a peak in the decrease between about 160 - 260 um
• difference in branch number is limited to third and fourth order branches
• however, the number of primary dendrites and the longest dendritic path from a cell are not different from wild-type controls
• following transection of the sciatic nerve in the right hindlimb uncontrolled sprouting is increased
• however, myelination following transection is not significantly different from controls
• following transection of the sciatic nerve in the right hindlimb time to recovery of motor function is delayed

muscle
• muscle atrophy induced by transection of the sciatic nerve in the right hindlimb is reduced
• attenuation of the beta-adrenergic inotropic responses indicating a decrease in myocardial contractile reserve
• isolated ventricular myocytes display greater overall shortening at all stimulation frequencies between 0.2 and 10 Hz
• shortening in response to beta-adrenergic stimulation is greatly enhanced
• time to 50% relaxation is increased

behavior/neurological
• when placed with females in estrus males display excessive and inappropriate mounting
• in a resident intruder assay males display more aggressive encounters and initiate more of the aggressive encounters compared to wild-type mice
• for males latency to first attack is reduced to about 1/5 that of wild-type mice
• male mice display submissive postures about 1/10 as frequently as wild-type controls
• for males the duration of aggressive encounters is increased
• no increase in aggression is seen in females
• when placed with females in estrus males display excessive and inappropriate mounting
• the number of mounts fails to decrease significantly 1 h after the introduction of an anestrus female to the cage
• by 7 to 8 h after introduction of a female, the number of mounts made by males is 2 to 3 times greater compared to wild-type males

homeostasis/metabolism
N
• despite the increase in aggressive and sexual behaviors, no significant difference is detected in blood testosterone levels compared to wild-type males
• in awake mice carbon dioxide production is significantly decreased during 12% oxygen compared to 100% oxygen in mutant but not in wild-type mice
• in awake mice the magnitude of the decrease in oxygen consumption under 21% or 12% oxygen is greater than that in wild-type controls
• sodium cyanide induced respiratory stimulation is increased in mutants compared to wild-type mice
• delay in Wallerian degeneration following transection of the sciatic nerve in the right hindlimb

respiratory system
• in awake mice the magnitude of the increases in tidal volume at 21% and 12% oxygen are greater than in wild-type controls
• anesthetized mice under 21% or 12% oxygen show period increases in respiratory rate not seen in wild-type mice
• in awake mice, the magnitude of the decrease in respiratory rate following brief exposure to 100% oxygen was greater than that in wild-type mice
• in awake and anesthetized mice the magnitude of the increases in respiratory rate at 21% and 12% oxygen are greater than in wild-type controls
• anesthetized mice do not display respiratory depression under 12% oxygen, unlike wild-type controls
• in anesthetized mutant mice the increase in ventilation under 21% oxygen results from an increase in both respiratory rate and tidal phrenic activity, unlike in wild-type mice where only tidal phrenic activity is increased
• sodium cyanide induced respiratory stimulation is increased in mutants compared to wild-type mice
• in awake mice the significant increases are seen in minute ventilation at both 21% and 12% oxygen unlike in wild-type controls where increases are seen only at 12% oxygen
• in awake and anesthetized mice the magnitude of the increase in minute ventilation is greater at both 21% and 12% oxygen compared to wild-type controls

cardiovascular system
• attenuation of the beta-adrenergic inotropic responses indicating a decrease in myocardial contractile reserve
• isolated ventricular myocytes display greater overall shortening at all stimulation frequencies between 0.2 and 10 Hz
• shortening in response to beta-adrenergic stimulation is greatly enhanced
• time to 50% relaxation is increased

cellular
• despite similar ratios of mitochondrial to nuclear DNA the amount of citrate synthase is significantly increased in homogenates from the heart, kidney and liver

liver/biliary system
• lipid content of the liver is increased (J:104558)
• unlike in wild-type livers, glycogen content is increased in zone 3 relative to zone 1 of the liver (J:133437)
• fat droplets are absent from the cytosol of hepatocytes

renal/urinary system
• electron microscopy analysis indicates a lower density of mitochondria in tubule cells of the kidney
• however, the ratio of mitochondrial to nuclear DNA is similar to controls

growth/size/body
N
• no difference in body weight is detected at 1 year of age


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)
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last database update
01/18/2022
MGI 6.17
The Jackson Laboratory