Phenotypes Associated with This Genotype

Genotype
MGI:2174975

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:106328 )

• in anesthetized mice under 12% oxygen all mutant mice survived while 4 of 14 wild-type mice died

decreased survivor rate ( J:129064 )

• survival at 20 months is reduced compared to Nos3 null mice

premature death ( J:16390 , J:129064 )

• 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

pyloric sphincter hypertrophy ( J:16390 )

pyloric stenosis ( J:16390 )

abnormal stomach wall morphology ( J:16390 )

• 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 smooth muscle circular layer hypertrophy ( J:16390 )

enlarged stomach ( J:16390 )

• stomach dilation, however architecture of the stomach layers is preserved

reproductive system

decreased ovulation rate ( J:89701 )

♀ • ovulatory efficiency (number oocytes recovered divided by the number of ovarian rupture sites) is reduced in homozygotes

decreased superovulation rate ( J:89701 )

♀ • significantly fewer oocytes are recovered following gonadotropin-stimulated ovulation in homozygous mutant females compared to wild-type females

nervous system

nervous system phenotype ( J:16390 )

N • homozygous mice do not exhibit defects in brain structure or neuron degeneration

slow Wallerian degeneration ( J:104916 )

• delay in Wallerian degeneration following transection of the sciatic nerve in the right hindlimb

abnormal brain morphology ( J:104558 )

• 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

abnormal motor neuron morphology ( J:111340 )

• 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

abnormal dendrite morphology ( J:111340 )

• 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

abnormal peripheral nervous system regeneration ( J:104916 )

• following transection of the sciatic nerve in the right hindlimb uncontrolled sprouting is increased

• however, myelination following transection is not significantly different from controls

delayed peripheral nervous system regeneration ( J:104916 )

• following transection of the sciatic nerve in the right hindlimb time to recovery of motor function is delayed

muscle

heart left ventricle hypertrophy ( J:75645 )

• age related

pyloric sphincter hypertrophy ( J:16390 )

stomach smooth muscle circular layer hypertrophy ( J:16390 )

abnormal muscle physiology ( J:104916 )

• muscle atrophy induced by transection of the sciatic nerve in the right hindlimb is reduced

decreased cardiac muscle contractility ( J:75645 )

• attenuation of the beta-adrenergic inotropic responses indicating a decrease in myocardial contractile reserve

increased heart ventricle muscle contractility ( J:103346 )

• 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

abnormal cardiac muscle relaxation ( J:103346 )

• time to 50% relaxation is increased

behavior/neurological

increased aggression towards female mice ( J:29970 )

• when placed with females in estrus males display excessive and inappropriate mounting

increased aggression towards male mice ( J:29970 )

• 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

abnormal mating frequency ( J:29970 )

• 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

homeostasis/metabolism phenotype ( J:29970 )

N • despite the increase in aggressive and sexual behaviors, no significant difference is detected in blood testosterone levels compared to wild-type males

abnormal carbon dioxide production ( J:106328 )

• in awake mice carbon dioxide production is significantly decreased during 12% oxygen compared to 100% oxygen in mutant but not in wild-type mice

abnormal oxygen consumption ( J:106328 )

• in awake mice the magnitude of the decrease in oxygen consumption under 21% or 12% oxygen is greater than that in wild-type controls

increased oxygen consumption ( J:106328 )

increased physiological sensitivity to xenobiotic ( J:106328 )

• sodium cyanide induced respiratory stimulation is increased in mutants compared to wild-type mice

slow Wallerian degeneration ( J:104916 )

• delay in Wallerian degeneration following transection of the sciatic nerve in the right hindlimb

respiratory system

increased tidal volume ( J:106328 )

• in awake mice the magnitude of the increases in tidal volume at 21% and 12% oxygen are greater than in wild-type controls

abnormal breathing pattern ( J:106328 )

• anesthetized mice under 21% or 12% oxygen show period increases in respiratory rate not seen in wild-type mice

abnormal pulmonary respiratory rate response ( J:106328 )

• 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

increased pulmonary respiratory rate ( J:106328 )

• 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

increased pulmonary ventilation ( J:106328 )

• 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

heart left ventricle hypertrophy ( J:75645 )

• age related

decreased cardiac muscle contractility ( J:75645 )

• attenuation of the beta-adrenergic inotropic responses indicating a decrease in myocardial contractile reserve

increased heart ventricle muscle contractility ( J:103346 )

• 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

abnormal cardiac muscle relaxation ( J:103346 )

• time to 50% relaxation is increased

cellular

abnormal mitochondrial physiology ( J:104558 )

• 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

abnormal liver morphology ( J:104558 , J:133437 )

• 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)

abnormal hepatocyte morphology ( J:133437 )

• fat droplets are absent from the cytosol of hepatocytes

renal/urinary system

abnormal renal tubule morphology ( J:104558 )

• 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

growth/size/body region phenotype ( J:133437 )

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

heart left ventricle hypertrophy ( J:75645 )

• age related

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic pyloric stenosis		DOID:12638	OMIM:179010 OMIM:300711 OMIM:610260 OMIM:612017 OMIM:612525	J:16390