Phenotypes associated with this allele

• Allele Symbol: Nos1^tm1Plh
• Allele Name: targeted mutation 1, Paul L Huang
• Allele ID: MGI:1857227
• Summary: 21 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nos1^tm1Plh/Nos1^tm1Plh	B6.129S4-Nos1^tm1Plh	MGI:3621555
hm2	Nos1^tm1Plh/Nos1^tm1Plh	B6;129S4-Nos1^tm1Plh/J	MGI:4367207
hm3	Nos1^tm1Plh/Nos1^tm1Plh	B6.129S4-Nos1^tm1Plh/J	MGI:4367210
hm4	Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae	MGI:3618910
hm5	Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366783
hm6	Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/6	MGI:2174975
hm7	Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/6J	MGI:4366780
ht8	Nos1^tm1Plh/Nos1^+	B6.129S4-Nos1^tm1Plh	MGI:4367227
cx9	Nos1^tm1Plh/Nos1^tm1Plh Nos3^tm1Plh/Nos3^tm1Plh	B6.129S4-Nos3^tm1Plh Nos1^tm1Plh	MGI:4367213
cx10	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Lau/Nos2^tm1Lau	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J	MGI:4367217
cx11	Nos1^tm1Plh/Nos1^tm1Plh Nos3^tm1Unc/Nos3^tm1Unc	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J	MGI:4367218
cx12	Hmox2^tm1Poss/Hmox2^tm1Poss Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S2/SvPas * 129S4/SvJae	MGI:4366930
cx13	Nos1^tm1Plh/Nos1^tm1Plh Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae	MGI:3789202
cx14	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3789201
cx15	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3789190
cx16	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6	MGI:4837924
cx17	Nos1^tm1Plh/Nos1^tm1Plh Tg(SOD1)76Dpr/0	involves: 129S4/SvJae * C3H/HeJ * C57BL/6 * C57BL/6J	MGI:4366928
cx18	Dmd^mdx/Dmd^+ Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366782
cx19	Dmd^mdx/Y Nos1^tm1Plh/Nos1^tm1Plh	involves: 129S4/SvJae * C57BL/10ScSn	MGI:4366781
cx20	Nos1^tm1Plh/Nos1^tm1Plh Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae * C57BL/6	MGI:4367214
cx21	Nos1^tm1Plh/Nos1^tm1Plh Tg(RHO-VEGFA)V-6Camp/0	involves: 129S4/SvJae * C57BL/6J	MGI:4366932

Genotype
MGI:3621555

hm1

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: B6.129S4-Nos1^tm1Plh

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

cardiovascular system

cardiovascular system phenotype ( J:106207 )

N • unlike mice null for Nos3, ischemia induced retinal neovascularization is not significantly different from controls

decreased susceptibility to induced choroidal neovascularization ( J:106207 )

• knockouts show a 58% decrease in neovascularization at sites of laser-induced Bruch's membrane rupture compared to heterozygous littermates

abnormal blood-brain barrier function ( J:150557 )

• kainic acid injection of hippocampi does not cause blood-brain barrier breakdown

behavior/neurological

behavior/neurological phenotype ( J:67776 )

N • Background Sensitivity: unlike mice on a mixed 129S4/SvJae and C57BL/6J background, congenic male mice do not display significantly increased aggression compared to wild-type controls

decreased aggression towards male mice ( J:57543 )

• lactating females display decreased aggression towards intruder males

• about a 90% decrease in the amount of time lactating females spend actively attacking or biting an intruder male

increased aggression towards male mice ( J:127032 )

• increase in the number and duration of attacks and decrease in the latency to attack in a resident intruder assay

• treatment with a serotonin precursor dramatically reduces aggressive behavior

• significantly higher concentrations of serotonin receptor agonists are required to reduce aggressive behavior than in wild-type controls

abnormal maternal behavior ( J:57543 )

♀ • lactating females display decreased aggression towards intruder males

♀ • about a 90% decrease in the amount of time lactating females spend actively attacking or biting an intruder male

♀ • in contrast to the decrease in maternal aggression, no defect in pup retrieval is detected

abnormal seizure response to inducing agent ( J:107964 )

• when exposed to hyperbaric oxygen (greater than 99% oxygen) at 5 ATA for 60 min the time to first seizure in freely moving mice is significantly longer compared to similarly treated wild-type mice

homeostasis/metabolism

decreased susceptibility to neuronal excitotoxicity ( J:150557 )

• kainic acid does not cause the hippocampal neurons to degenerate

increased circulating triglyceride level ( J:155090 )

• elevated plasma triglycerides

decreased adiponectin level ( J:155090 )

abnormal serotonin level ( J:127032 )

• total serotonin content is increased in the cerebral cortex, hypothalamus, hippocampus, midbrain and cerebellum

• as no change is seen on the concentration of the serotonin metabolite, 5-HIAA, the 5-HIAA to serotonin (5-HT) ratio is reduced in the cortex, hypothalamus, midbrain, and cerebellum indicating a decrease in serotonin turnover

decreased susceptibility to ischemic brain injury ( J:128835 )

• functional deficits following middle cerebral artery obstruction are reduced compared to wild-type controls

decreased cerebral infarct size ( J:128835 )

• infarction sized induced by middle cerebral artery obstruction is reduced in males, but not in females, compared to wild-type controls

• however, infarct size is increased compared to mice hemizygous for Tg(SOD1)76Dpr

vision/eye

decreased susceptibility to induced choroidal neovascularization ( J:106207 )

• knockouts show a 58% decrease in neovascularization at sites of laser-induced Bruch's membrane rupture compared to heterozygous littermates

nervous system

abnormal nervous system physiology ( J:107964 )

• in anesthetized mice the latency to hyperbaric oxygen (greater than 99% oxygen) at 5 ATA induced EEG seizure is increased compared to similarly treated wild-type mice

• striatal accumulation of 3-nitrotyrosine during hyperbaric oxygen exposure is decreased compared to similarly treated wild-type mice

abnormal seizure response to inducing agent ( J:107964 )

• when exposed to hyperbaric oxygen (greater than 99% oxygen) at 5 ATA for 60 min the time to first seizure in freely moving mice is significantly longer compared to similarly treated wild-type mice

abnormal blood-brain barrier function ( J:150557 )

• kainic acid injection of hippocampi does not cause blood-brain barrier breakdown

decreased susceptibility to neuronal excitotoxicity ( J:150557 )

• kainic acid does not cause the hippocampal neurons to degenerate

decreased susceptibility to ischemic brain injury ( J:128835 )

• functional deficits following middle cerebral artery obstruction are reduced compared to wild-type controls

decreased cerebral infarct size ( J:128835 )

• infarction sized induced by middle cerebral artery obstruction is reduced in males, but not in females, compared to wild-type controls

• however, infarct size is increased compared to mice hemizygous for Tg(SOD1)76Dpr

cellular

decreased susceptibility to neuronal excitotoxicity ( J:150557 )

• kainic acid does not cause the hippocampal neurons to degenerate

maternal effect ( J:57543 )

• pups of homozygous females weigh more than pups of wild-type females

Genotype
MGI:4367207

hm2

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: B6;129S4-Nos1^tm1Plh/J

behavior/neurological

behavior/neurological phenotype ( J:83571 )

N • increased aggressive behavior is not seen in males unlike in other reports

abnormal sleep pattern ( J:83571 )

• mice spend less time in REM sleep as a result of fewer REM episodes and lengthened duration of the inter REM intervals

• however, there is no significant difference in the amount of time spent in non-REM sleep and mice display normal diurnal variation in sleep patterns

nervous system

abnormal brain wave pattern ( J:83571 )

• during non-REM sleep the absolute value of slow wave activity is increased

skeleton

increased bone mineral content ( J:105612 )

• bone mineral content is increased

increased bone mineral density ( J:105612 )

• bone mineral density is increased

abnormal trabecular bone morphology ( J:105612 )

• trabecular bone tends to extend deeper into the metaphysis

increased trabecular bone volume ( J:105612 )

increased trabecular bone thickness ( J:105612 )

abnormal skeleton development ( J:105612 )

• indices of bone formation and resorption are lower

abnormal osteoclast differentiation ( J:105612 )

• in culture RANKL and M-CSF induced osteoclast formation are increased

hematopoietic system

abnormal osteoclast differentiation ( J:105612 )

• in culture RANKL and M-CSF induced osteoclast formation are increased

immune system

abnormal osteoclast differentiation ( J:105612 )

• in culture RANKL and M-CSF induced osteoclast formation are increased

cellular

abnormal osteoclast differentiation ( J:105612 )

• in culture RANKL and M-CSF induced osteoclast formation are increased

Genotype
MGI:4367210

hm3

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: B6.129S4-Nos1^tm1Plh/J

growth/size/body

decreased body weight ( J:144588 )

• in males only

muscle

decreased skeletal muscle weight ( J:144588 )

• decrease in skeletal muscle weight in males

impaired skeletal muscle contractility ( J:144588 )

• peak twitch force is decreased in the tibialis anterior muscle of male mice

• decrease in the maximal tetanic force generating capacity of the tibialis anterior muscle in males

• however, when normalized to muscle size the force generating capacity is not significantly different from wild-type controls

increased muscle fatigability ( J:144588 )

• tibialis anterior muscle displays an increase in the susceptibility to contraction induced fatigue in both males and females

immune system

decreased inflammatory response ( J:103018 )

• fever in response to LPS injection is partially reduced compared to wild-type controls

• reduction in fever response mainly occurs during the early phase of fever response

• however, fever in response to turpentine injection is not different from controls

Genotype
MGI:3618910

hm4

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

mortality/aging

decreased survivor rate ( J:100308 )

• about 80% survival rate at 10 months of age

premature death ( J:100308 )

• about 20% die before 10 months of age

homeostasis/metabolism

abnormal response of heart to induced stress ( J:60525 )

• myocardial infarct size following 30 min of global ischemia is increased compared to controls

abnormal vascular wound healing ( J:120009 )

• following carotid artery ligation the extent of neointimal formation is increased and luminal narrowing is worsened compared to wild-type controls

decreased susceptibility to neuronal excitotoxicity ( J:111644 )

• the size of striatal lesions induced by malonate are significantly reduced compared to similarly treated controls

insulin resistance ( J:62229 )

• insulin resistance in peripheral tissues

decreased susceptibility to injury ( J:93439 )

• 24 h after aspiration bulbectomy the number of apoptotic cells in the piriform cortex is reduced compared to similarly treated wild-type mice

decreased cerebral infarct size ( J:127062 )

• following occlusion of the middle cerebral artery infarct size is decreased

nervous system

nervous system phenotype ( J:37956 , J:84255 )

N • despite the ability of NOS inhibitors to decrease long term potentiation, no significant decrease in long term potentiation is detected at 1 h after tetanus (J:37956)

N • unlike cerebral blood flow, the intensity of neural activation induced by perioral stimulation is not significantly different from controls (J:84255)

abnormal nervous system physiology ( J:93439 )

• 24 h after aspiration bulbectomy the number of apoptotic cells in the piriform cortex is reduced compared to similarly treated wild-type mice

decreased susceptibility to neuronal excitotoxicity ( J:111644 )

• the size of striatal lesions induced by malonate are significantly reduced compared to similarly treated controls

decreased cerebral infarct size ( J:127062 )

• following occlusion of the middle cerebral artery infarct size is decreased

abnormal long-term potentiation ( J:19282 )

• following a theta burst protocol at a weak intensity enhancement of EPSPs during the first 3 minutes after stimulation is significantly small compared to controls

• however, no significant differences are detected when a stronger intensity stimulation is used

absent long-term depression ( J:42548 )

• stimulation of parallel fibers with a 50 msec postsynaptic depolarizations fails to induce long term depression in Purkinje cells

• addition of uncaged NO or photoreleased cGMP to the stimulation protocol also fails to induce long term depression in Purkinje cells, unlike in wild-type mice

decreased synaptic glutamate release ( J:119052 )

• glutamate release after NMDA stimulation is significantly attenuated in the cerebral cortex, partially reduced in the striatum but unaffected in the hippocampus

behavior/neurological

behavior/neurological phenotype ( J:42548 , J:56005 )

N • unlike in earlier reports males show no signs of increased aggression (J:42548)

N • no defects in circadian rhythms are detected in a wheel running assay either under entrained or free running conditions (J:56005)

impaired balance ( J:56005 )

• mice show no improvement in their latency to fall off a pole or plank in the dark versus the light phase, unlike in wild-type controls resulting in deficits in balance compared to wild-type mice during the dark phase

digestive/alimentary system

abnormal gastroesophageal sphincter physiology ( J:56948 , J:70182 )

• lower esophageal sphincters fail to display electrical field stimulation (60 V, 5 Hz) induced relaxation or rebound contraction (J:56948)

• the mean resting lower esophageal sphincter pressure is significantly higher (J:70182)

• swallowing induced lower esophageal sphincter relaxation is significantly attenuated (J:70182)

• mice show a range of responses to pharyngeal stimulation including no relaxation, partial relaxation , and sporadic near complete relaxation of the lower esophageal sphincter (J:70182)

• efferent vagal stimulation induced lower esophageal sphincter relaxation is significantly attenuated (J:70182)

immune system

abnormal leukocyte adhesion ( J:55936 )

• dramatic increase in baseline leukocyte adherence

• treatment with an anti-P-selectin antibody significantly reduces the adhesion response in mutant but not in wild-type mice

enhanced leukocyte tethering or rolling ( J:55936 )

• increase in baseline rolling

• treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice

• treatment with a low dose of thrombin significantly increases rolling in mutant but not in wild-type mice

abnormal neutrophil physiology ( J:55936 )

• following thioglycollate injection neutrophil accumulation in the peritoneum is significantly enhanced compared to wild-type mice

muscle

abnormal muscle physiology ( J:89581 )

• the resting membrane potential of jejunal smooth muscle cells is depolarized about 5 mV compared to wild type cells

• hyperpolarization and induction of an inhibitory junction potential in response to electrical field stimulation under nonadrenergic noncholinergic conditions in jejunal muscle strips are markedly reduced

abnormal gastroesophageal sphincter physiology ( J:56948 , J:70182 )

• lower esophageal sphincters fail to display electrical field stimulation (60 V, 5 Hz) induced relaxation or rebound contraction (J:56948)

• the mean resting lower esophageal sphincter pressure is significantly higher (J:70182)

• swallowing induced lower esophageal sphincter relaxation is significantly attenuated (J:70182)

• mice show a range of responses to pharyngeal stimulation including no relaxation, partial relaxation , and sporadic near complete relaxation of the lower esophageal sphincter (J:70182)

• efferent vagal stimulation induced lower esophageal sphincter relaxation is significantly attenuated (J:70182)

abnormal muscle relaxation ( J:56948 , J:89581 )

• lower esophageal sphincters fail to display electrical field stimulation (60 V, 5 Hz) induced relaxation or rebound contraction (J:56948)

• the decrease in muscle contractions in jejunal muscle strips in response to electrical field stimulation is markedly reduced (J:89581)

cardiovascular system

cardiovascular system phenotype ( J:57624 )

N • unlike in mice null for Nos3 no significant abnormalities in hypoxic pulmonary vasoconstriction, vasodilation in response to bradykinin, or right ventricle systolic pressure are detected

decreased heart weight ( J:60525 )

abnormal cerebral blood flow rate ( J:84255 )

• the increase in cerebral blood flow induced by glutamate, perioral stimulation, or harmaline is significantly attenuated

decreased coronary flow rate ( J:60525 )

• in isolated perfused hearts

• however, coronary flow per beat is not significantly different from controls

abnormal response of heart to induced stress ( J:60525 )

• myocardial infarct size following 30 min of global ischemia is increased compared to controls

abnormal vascular wound healing ( J:120009 )

• following carotid artery ligation the extent of neointimal formation is increased and luminal narrowing is worsened compared to wild-type controls

vision/eye

vision/eye phenotype ( J:56005 )

N • no defects are detected in visual acuity

reproductive system

reproductive system phenotype ( J:89704 )

N • unlike in Nos3 null mice, the increase in maximal penile intracavernous pressure induced by papaverine is not significantly different from wild-type controls

growth/size/body

decreased body weight ( J:60525 )

cellular

decreased susceptibility to neuronal excitotoxicity ( J:111644 )

• the size of striatal lesions induced by malonate are significantly reduced compared to similarly treated controls

abnormal leukocyte adhesion ( J:55936 )

• dramatic increase in baseline leukocyte adherence

• treatment with an anti-P-selectin antibody significantly reduces the adhesion response in mutant but not in wild-type mice

enhanced leukocyte tethering or rolling ( J:55936 )

• increase in baseline rolling

• treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice

• treatment with a low dose of thrombin significantly increases rolling in mutant but not in wild-type mice

hematopoietic system

abnormal leukocyte adhesion ( J:55936 )

• dramatic increase in baseline leukocyte adherence

• treatment with an anti-P-selectin antibody significantly reduces the adhesion response in mutant but not in wild-type mice

enhanced leukocyte tethering or rolling ( J:55936 )

• increase in baseline rolling

• treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice

• treatment with a low dose of thrombin significantly increases rolling in mutant but not in wild-type mice

abnormal neutrophil physiology ( J:55936 )

• following thioglycollate injection neutrophil accumulation in the peritoneum is significantly enhanced compared to wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achalasia		DOID:9164	OMIM:200400	J:70182

Genotype
MGI:4366783

hm5

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

muscle phenotype ( J:48851 )

N • no abnormalities in muscle morphology are detected

Genotype
MGI:2174975

hm6

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

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

Genotype
MGI:4366780

hm7

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

renal/urinary system

increased urine bicarbonate level ( J:64896 )

• increase in urine bicarbonate concentration

increased urine pH ( J:64896 )

• increase in urine pH

abnormal renal reabsorption ( J:64896 )

• the rate of bicarbonate absorption is reduced in the proximal tubules

abnormal renal water reabsorption ( J:64896 )

• the rate of net fluid absorption is reduced in the proximal tubules

cardiovascular system

increased heart rate ( J:108674 )

• atria display higher baseline heart rates

• decrease in heart rate in response to vagal nerve stimulation is slower

decreased mean systemic arterial blood pressure ( J:64896 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:79215 )

N • despite differences in behavioral responses to alcohol, no differences in blood alcohol elimination are detected

abnormal renal water reabsorption ( J:64896 )

• the rate of net fluid absorption is reduced in the proximal tubules

increased urine bicarbonate level ( J:64896 )

• increase in urine bicarbonate concentration

metabolic acidosis ( J:64896 )

• arterial blood pH and bicarbonate concentrations are reduced resulting in a modest but significant metabolic acidosis

increased urine pH ( J:64896 )

• increase in urine pH

behavior/neurological

increased alcohol consumption ( J:79215 )

• mice consume more alcohol when presented with solutions containing high concentrations of alcohol (greater than 8% alcohol) compared to wild-type controls

• however, when presented with dilute solutions of alcohol (2 - 4%), alcohol consumption does not differ from controls

abnormal behavioral response to addictive substance ( J:79215 )

• following dosing with 2.5 or 4.5 gm/kg mice regain their righting reflex faster compared to similarly treated wild-type controls

enhanced behavioral response to addictive substance ( J:79215 )

• mice fail to develop tolerance to alcohol induced hypothermia following multiple ethanol injection

abnormal spatial learning ( J:101815 )

• impaired performance during memory recall trials in a Morris water maze

• however, performance in the less stressful multiple T maze is improved compared to controls

abnormal liquid preference ( J:79215 )

• the concentration dependent increase in sucrose preference is more pronounced in mutants compared to wild-type controls

• however, the concentration dependent aversion to quinine is not significantly different from controls

increased aggression towards male mice ( J:67776 )

• Background Sensitivity: unlike mice on a congenic C57BL/6J background, male mice display increased aggression

• Background Sensitivity: mice display increased aggression compared to C57BL/6J mice but not compared to 129S2/SvPas mice

increased coping response ( J:101815 )

• in a forced swim test mice spend more time actively swimming and less time immobile compared to wild-type controls

increased anxiety-related response ( J:101815 )

• increase in grooming behavior is seen in mice in an open field and during an elevated plus maze assay suggesting an increase in the amount of stress mice experience under these conditions

increased grooming behavior ( J:101815 )

• seen in mice in an open field and during an elevated plus maze assay suggesting an increase in the amount of stress mice experience under these conditions

enhanced coordination ( J:101815 )

• in the last trial mice spend more time on the rotarod compared to wild-type controls

digestive/alimentary system

digestive/alimentary phenotype ( J:64225 )

N • unlike in human patients with Infantile Hypertrophic Pyloric Stenosis, the luminal aperture of the pyloric sphincter is not significantly smaller in relaxed tissues compared to wild type controls

enlarged esophagus ( J:64225 )

• diffuse enlargement

enlarged duodenum ( J:64225 )

• diffuse enlargement

pyloric sphincter hypertrophy ( J:64225 )

• pyloric sphincter thickness is increased by 17% compared to controls

enlarged stomach ( J:64225 )

• diffuse enlargement

• weight and volume are increased

gastric hypertrophy ( J:64225 )

• muscular thickening is seen throughout the stomach

abnormal digestion ( J:64225 )

• stomachs often contain bezoars even after 2 days of fasting

impaired gastric peristalsis ( J:64225 )

• gastric emptying of solids and liquids is delayed

muscle

pyloric sphincter hypertrophy ( J:64225 )

• pyloric sphincter thickness is increased by 17% compared to controls

growth/size/body

enlarged esophagus ( J:64225 )

• diffuse enlargement

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	hypertrophic pyloric stenosis	DOID:12638	OMIM:179010 OMIM:300711 OMIM:610260 OMIM:612017 OMIM:612525	J:64225

Genotype
MGI:4367227

ht8

• Allelic Composition: Nos1^tm1Plh/Nos1⁺
• Genetic Background: B6.129S4-Nos1^tm1Plh

cardiovascular system

abnormal cardiovascular system physiology ( J:105579 )

• exercise training fails to augment the phenylephrine induced pulse interval response

abnormal heart rate ( J:105579 )

• exercise training fails to augment the phenylephrine induced or vagal nerve stimulation bradycardia responses

• no differences in heart rate responses are detected in the absence of exercise training

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:105579 )

• exercise training fails to augment the phenylephrine induced bradycardia and pulse interval responses

• no differences in phenylephrine induced responses are seen in untrained mice

Genotype
MGI:4367213

cx9

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos3^tm1Plh/Nos3^tm1Plh
• Genetic Background: B6.129S4-Nos3^tm1Plh Nos1^tm1Plh

cardiovascular system

heart left ventricle hypertrophy ( J:129064 )

• myocyte hypertrophy is detected by 4-5 months of age

• hypertrophy becomes more severe with age

cardiac interstitial fibrosis ( J:129064 )

• areas of focal interstitial fibrosis are seen in old (14-15 months of age) mice

increased cardiac muscle contractility ( J:129064 )

• prior to the development of frank left ventricular hypertrophy indices of myocardial contractility are elevated

• indices of contractility are also increased in old mice

• ejection fraction is increased in old mice

abnormal cardiac muscle relaxation ( J:129064 )

• passive diastolic relaxation appears impaired based on an increase in the time to peak filling

decreased left ventricle diastolic pressure ( J:129064 )

• decrease in left ventricular end diastolic pressure in young mice

increased heart rate ( J:129064 )

increased systemic arterial systolic blood pressure ( J:129064 )

• in young and old mice

muscle

heart left ventricle hypertrophy ( J:129064 )

• myocyte hypertrophy is detected by 4-5 months of age

• hypertrophy becomes more severe with age

increased cardiac muscle contractility ( J:129064 )

• prior to the development of frank left ventricular hypertrophy indices of myocardial contractility are elevated

• indices of contractility are also increased in old mice

• ejection fraction is increased in old mice

abnormal cardiac muscle relaxation ( J:129064 )

• passive diastolic relaxation appears impaired based on an increase in the time to peak filling

growth/size/body

heart left ventricle hypertrophy ( J:129064 )

• myocyte hypertrophy is detected by 4-5 months of age

• hypertrophy becomes more severe with age

cellular

cardiac interstitial fibrosis ( J:129064 )

• areas of focal interstitial fibrosis are seen in old (14-15 months of age) mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy		DOID:11984		J:129064

Genotype
MGI:4367217

cx10

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos2^tm1Lau/Nos2^tm1Lau
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J

mortality/aging

prenatal lethality, incomplete penetrance ( J:83112 )

• fewer than expected double homozygotes are born, no time of lethality provided

Genotype
MGI:4367218

cx11

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos3^tm1Unc/Nos3^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J

mortality/aging

prenatal lethality, incomplete penetrance ( J:83112 )

• fewer than expected double homozygotes are born, no time of lethality provided

Genotype
MGI:4366930

cx12

• Allelic Composition: Hmox2^tm1Poss/Hmox2^tm1Poss; Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae

muscle

abnormal muscle physiology ( J:89581 )

• the resting membrane potential of jejunal smooth muscle cells is depolarized about 13 mV compared to wild type cells

• hyperpolarization and induction of an inhibitory junction potential in response to electrical field stimulation in jejunal muscle strips are markedly reduced

• unlike in wild-type controls electrical field stimulation under nonadrenergic noncholinergic conditions induces a depolarization of membrane potential in jejunal smooth muscle cells

abnormal muscle relaxation ( J:89581 )

• the decrease in muscle contractions in jejunal muscle strips in response to electrical field stimulation is markedly reduced

Genotype
MGI:3789202

cx13

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos3^tm1Plh/Nos3^tm1Plh
• Genetic Background: involves: 129S4/SvJae

mortality/aging

decreased survivor rate ( J:100308 )

• 60-80% survival rate at 10 months of age

premature death ( J:100308 )

• about 20-40% die before 10 months of age

reproductive system

reduced fertility ( J:100308 )

• slight reduction in the number of offspring produced from breeding pairs

cardiovascular system

decreased heart rate ( J:100308 )

increased systemic arterial systolic blood pressure ( J:100308 )

homeostasis/metabolism

increased blood osmolality ( J:100308 )

increased blood urea nitrogen level ( J:100308 )

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

behavior/neurological

polydipsia ( J:100308 )

nervous system

nervous system phenotype ( J:37956 )

N • unlike long term potentiation, long term depression and paired pulse facilitation are not significantly different from controls and no significant abnormalities in hippocampal morphology are detected

abnormal sensory neuron innervation pattern ( J:61144 )

• at P21 the ipsilateral retinocollicular projections are spread across cover more of the medio-lateral axis of and extend further caudally in the superior colliculus rather than being confined to the most medial and rostral regions as in wild-type controls

• at P28, ipsilateral retinocollicular projections remain more broadly distributed in the superior colliculus

• however, by P90 ipsilateral retinocollicular projections resemble those in wild-type controls indicating a delay in refinement rather than a block

reduced long-term potentiation ( J:37956 )

• unlike in either single homozygote, hippocampal long term potentiation is significantly reduced at 1 h after tetanus

• however, long term potentiation in the stratum oriens is not significantly different from controls

renal/urinary system

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

polyuria ( J:100308 )

Genotype
MGI:3789201

cx14

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd

mortality/aging

decreased survivor rate ( J:100308 )

• 60-80% survival rate at 10 months of age

premature death ( J:100308 )

• about 20-40% die before 10 months of age

reproductive system

reduced fertility ( J:100308 )

• slight reduction in the number of offspring produced from breeding pairs

homeostasis/metabolism

increased blood osmolality ( J:100308 )

• plasma osmolality is increased

increased blood urea nitrogen level ( J:100308 )

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

renal/urinary system

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

polyuria ( J:100308 )

behavior/neurological

polydipsia ( J:100308 )

Genotype
MGI:3789190

cx15

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos2^tm1Mrl/Nos2^tm1Mrl; Nos3^tm1Plh/Nos3^tm1Plh
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd

Renal tubular apoptosis, regeneration, glomerulosclerosis and glomerular thrombus formation in Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl Nos3^tm1Plh/Nos3^tm1Plh mice

mortality/aging

decreased survivor rate ( J:100308 )

• only 3 of 13 mutants survive to 10 months of age

premature death ( J:100308 )

• only 3 of 13 mutants survive to 10 months of age

reproductive system

reduced fertility ( J:100308 )

• the number of offspring produced from breeding pairs is significantly smaller than in wild-type

cardiovascular system

abnormal coronary artery morphology ( J:100308 )

• all mutants that die show wall thickening, perivascular fibrosis, and adventitial mast cell infiltration of the coronary arteries

visceral vascular congestion ( J:100308 )

• 2 mutants that die within 10 months of age, have pulmonary and liver congestion

liver vascular congestion ( J:100308 )

• in 2 mutants that die within 10 months of age

pulmonary vascular congestion ( J:100308 )

• in 2 mutants that die within 10 months of age

decreased heart rate ( J:100308 )

• heart rate is significantly lower than in wild-type, but similar to that of single Nos3 homozygotes, double Nos1/Nos3 homozygotes, and double Nos2/Nos3 homozygotes

increased systemic arterial blood pressure ( J:100308 )

hypertension ( J:100308 )

• hypertension is similar to single Nos3 homozygotes, double Nos1/Nos3 homozygotes, and double Nos2/Nos3 homozygotes

increased systemic arterial systolic blood pressure ( J:100308 )

• systolic blood pressure is significantly higher in mutants than wild-type under conscious conditions

congestive heart failure ( J:100308 )

• the two mutants with pulmonary and liver congestion and acute renal tubular necrosis exhibit acute circulatory failure

homeostasis/metabolism

increased circulating creatinine level ( J:100308 )

• plasma concentrations of creatinine tend to be higher

increased blood osmolality ( J:100308 )

• plasma osmolality is increased

increased blood urea nitrogen level ( J:100308 )

• plasma concentrations of urea nitrogen are higher

increased circulating alkaline phosphatase level ( J:150159 )

• serum concentration is increased

abnormal glomerular capillary thrombosis ( J:100308 )

• glomerular thrombus formation

dehydration ( J:100308 )

abnormal nitric oxide homeostasis ( J:100308 )

• mutants exhibit only 2.4% and 3.6% of normal plasma and urinary NO levels, respectively

decreased urine sodium level ( J:100308 )

increased prostaglandin level ( J:100308 )

• renal prostacyclin levels are significantly higher in 1 week old mutants than in wild-type

decreased urine osmolality ( J:100308 )

renal/urinary system

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

abnormal renal glomerulus morphology ( J:100308 )

• glomerular thrombus formation

• renal tubular lesions are seen predominantly in distal and collecting tubules than in proximal tubules

glomerulosclerosis ( J:100308 )

renal tubular necrosis ( J:100308 )

• 2 mutants that die within 10 months of age have acute renal tubular necrosis

abnormal kidney physiology ( J:100308 )

• renal responsiveness to the anti-diuretic hormone, vasopressin, is reduced compared to wild-type, although central vasopressin release in unchanged

• impaired renal cAMP production

increased renal tubule apoptosis ( J:100308 )

polyuria ( J:100308 )

• hypotonic polyuria

behavior/neurological

polydipsia ( J:100308 )

digestive/alimentary system

pyloric sphincter hypertrophy ( J:100308 )

• pyloric sphincter hypertrophy

enlarged stomach ( J:100308 )

• 3 of 5 mutants show enlargement of the stomach

liver/biliary system

liver vascular congestion ( J:100308 )

• in 2 mutants that die within 10 months of age

respiratory system

pulmonary vascular congestion ( J:100308 )

• in 2 mutants that die within 10 months of age

skeleton

abnormal bone structure ( J:150159 )

increased osteoclast cell number ( J:150159 )

increased bone mineral density ( J:150159 )

• at all time points

• increases slightly at 12 weeks of age

abnormal trabecular bone morphology ( J:150159 )

• trabecular bone in the proximal tibia is increased

abnormal skeleton physiology ( J:150159 )

abnormal osteoclast physiology ( J:150159 )

• increased osteoclast function

• higher in females than in males

abnormal bone mineralization ( J:150159 )

• bone formation rate and mineral apposition rate are increased

• higher in females than in males

hematopoietic system

increased osteoclast cell number ( J:150159 )

abnormal osteoclast physiology ( J:150159 )

• increased osteoclast function

• higher in females than in males

immune system

increased osteoclast cell number ( J:150159 )

abnormal osteoclast physiology ( J:150159 )

• increased osteoclast function

• higher in females than in males

muscle

pyloric sphincter hypertrophy ( J:100308 )

• pyloric sphincter hypertrophy

cellular

increased renal tubule apoptosis ( J:100308 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrogenic diabetes insipidus		DOID:12387		J:100308

Genotype
MGI:4837924

cx16

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos2^tm1Mrl/Nos2^tm1Mrl; Nos3^tm1Plh/Nos3^tm1Plh
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:155090 )

• 85% of males die within 11 months whereas only 35-40% of males of any double homozygous genotype die at that time point

cardiovascular system

abnormal cardiovascular system morphology ( J:155090 )

arteriosclerosis ( J:155090 )

• in most of the vasculature

• lipid accumulation in the aorta

perivascular fibrosis ( J:155090 )

• perivascular fibrosis of large epicardial coronary arteries and renal arteries

thick ventricular wall ( J:155090 )

• anterior and posterior ventricular walls are thickened

abnormal cardiovascular system physiology ( J:155090 )

hypertension ( J:155090 )

abnormal vascular endothelial cell physiology ( J:155090 )

• endothelium dependent relaxation lacking

abnormal vascular wound healing ( J:155090 )

• no vascular lesions in 2 month old males

• significant neointimal formation at 5 months

• medial thickening at 5 months

adipose tissue

increased white adipose tissue amount ( J:155090 )

• perirenal and epididymal white adipose weights are increased

homeostasis/metabolism

abnormal vascular wound healing ( J:155090 )

• no vascular lesions in 2 month old males

• significant neointimal formation at 5 months

• medial thickening at 5 months

abnormal circulating glucose level ( J:155090 )

• significantly increased after i.v. glucose

increased circulating LDL cholesterol level ( J:155090 )

increased circulating triglyceride level ( J:155090 )

• elevated plasma triglycerides

decreased adiponectin level ( J:155090 )

Genotype
MGI:4366928

cx17

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Tg(SOD1)76Dpr/0
• Genetic Background: involves: 129S4/SvJae * C3H/HeJ * C57BL/6 * C57BL/6J

nervous system

decreased susceptibility to ischemic brain injury ( J:128835 )

• functional deficits following middle cerebral artery obstruction are reduced compared to wild-type controls but not compared to mice hemizygous for Tg(SOD1)76Dpr alone

decreased cerebral infarct size ( J:128835 )

• infarction sized induced by middle cerebral artery obstruction is reduced compared to wild-type controls

• however, the reduction in infarction size is not significantly different from that seen in mice hemizygous for Tg(SOD1)76Dpr alone

homeostasis/metabolism

decreased susceptibility to ischemic brain injury ( J:128835 )

• functional deficits following middle cerebral artery obstruction are reduced compared to wild-type controls but not compared to mice hemizygous for Tg(SOD1)76Dpr alone

decreased cerebral infarct size ( J:128835 )

• infarction sized induced by middle cerebral artery obstruction is reduced compared to wild-type controls

• however, the reduction in infarction size is not significantly different from that seen in mice hemizygous for Tg(SOD1)76Dpr alone

Genotype
MGI:4366782

cx18

• Allelic Composition: Dmd^mdx/Dmd⁺; Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

dystrophic muscle ( J:48851 )

♀ • mice show isolated dystrophic changes in the muscle

homeostasis/metabolism

abnormal circulating pyruvate kinase level ( J:48851 )

♀ • moderate elevation of pyruvate kinase levels is detectable by P21, absence of Nos1 expression does not significantly change pyruvate kinase levels compared to mice heterozygous for both Dmd^mdx and Nos1^tm1Plh

Genotype
MGI:4366781

cx19

• Allelic Composition: Dmd^mdx/Y; Nos1^tm1Plh/Nos1^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/10ScSn

muscle

dystrophic muscle ( J:48851 )

♂ • mice show severe dystrophic changes in the muscle

homeostasis/metabolism

abnormal circulating pyruvate kinase level ( J:48851 )

♂ • marked elevation of pyruvate kinase levels is detectable by P21, absence of Nos1 expression does not significantly change pyruvate kinase levels compared to mice hemizygous for Dmd^mdx and heterozygous for Nos1^tm1Plh

Genotype
MGI:4367214

cx20

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos3^tm1Plh/Nos3^tm1Plh
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

decreased survivor rate ( J:129064 )

• survival at 20 months is reduced compared to Nos3 or Nos1 single mutant mice

premature death ( J:129064 )

• survival at 20 months is reduced compared to Nos3 or Nos1 single mutant mice

• the relative risk of death by 20 months of age is increased 7.3 fold compared to Nos3 single mutants and 3.0 fold compared to Nos1 single mutants

• mortality is increased in males compared to females

cardiovascular system

heart left ventricle hypertrophy ( J:75645 )

• develop age related concentric remodeling with marked increase in relative wall thickness

• increase in wall thickness and decrease in systolic and diastolic dimensions with age

decreased cardiac muscle contractility ( J:75645 )

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

increased cardiac muscle contractility ( J:75645 )

• increase in basal contractility

• hypertrophy is associated with hypercontractility

abnormal cardiac muscle relaxation ( J:75645 )

• hypertrophy is associated with increased diastolic stiffness

increased heart rate ( J:75645 )

• relative to wild-type mice and Nos3 single mutants

increased systemic arterial systolic blood pressure ( J:75645 )

• identical to that in Nos3 single mutants

muscle

heart left ventricle hypertrophy ( J:75645 )

• develop age related concentric remodeling with marked increase in relative wall thickness

• increase in wall thickness and decrease in systolic and diastolic dimensions with age

decreased cardiac muscle contractility ( J:75645 )

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

increased cardiac muscle contractility ( J:75645 )

• increase in basal contractility

• hypertrophy is associated with hypercontractility

abnormal cardiac muscle relaxation ( J:75645 )

• hypertrophy is associated with increased diastolic stiffness

growth/size/body

heart left ventricle hypertrophy ( J:75645 )

• develop age related concentric remodeling with marked increase in relative wall thickness

• increase in wall thickness and decrease in systolic and diastolic dimensions with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy		DOID:11984		J:129064

Genotype
MGI:4366932

cx21

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Tg(RHO-VEGFA)V-6Camp/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

cardiovascular system

abnormal angiogenesis ( J:106207 )

• compared to mice carrying Tg(RHO-VEGFA)V-6Camp and heterozygous for Nos1^tm1Plh neovascularization of the retina is significantly reduced