Phenotypes Associated with This Genotype

Genotype
MGI:2174979

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

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

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

cardiovascular system

abnormal blood flow velocity ( J:112419 )

• decrease in lower thoracic aortic flow

decreased coronary flow rate ( J:60525 )

• in isolated perfused hearts

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

abnormal pulmonary vascular resistance ( J:112419 )

• total pulmonary resistance and pulmonary vascular resistance are increased

abnormal systemic vascular resistance ( J:112419 )

• acetylcholine fails to decrease total systemic resistance unlike in wild-type mice

abnormal heart right ventricle pressure ( J:57624 , J:100308 )

• increase in right ventricle systolic pressure in mice exposed to chronic mild hypoxia compared to similarly treated wild-type controls (J:57624)

decreased heart rate ( J:60525 , J:100308 )

• in isolated perfused hearts (J:60525)

increased heart rate ( J:112419 )

abnormal pulmonary pressure ( J:57624 )

• in isolated whole lungs baseline pulmonary perfusion pressure is increased compared to wild-type controls

pulmonary hypertension ( J:112419 )

• mild

abnormal systemic arterial blood pressure ( J:112419 )

• acetylcholine induced decrease in systemic arterial pressure is less than in wild-type controls

increased systemic arterial blood pressure ( J:57624 )

hypertension ( J:28778 , J:60525 )

increased mean systemic arterial blood pressure ( J:55936 )

increased vasoconstriction ( J:57624 )

• enhanced hypoxic pulmonary vasoconstriction

• treatment with bradykinin results in transient vasodilation followed by sustained vasoconstriction, while in wild-type mice vasodilation is maintained

abnormal vasodilation ( J:112419 )

• acetylcholine addition fails to induce any response in pulmonary artery segments, unlike in pulmonary artery segments from wild-type mice where it induces vasodilation

decreased vasodilation ( J:28778 )

• aortic rings show no relaxation to acetylcholine as in wild-type

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:111644 )

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

insulin resistance ( J:62229 )

• insulin resistance in the liver and peripheral tissues

abnormal response/metabolism to endogenous compounds ( J:112419 )

• acetylcholine induced decrease in systemic arterial pressure is less than in wild-type controls

• acetylcholine fails to decrease total systemic resistance unlike in wild-type mice

• acetylcholine addition fails to induce any response in pulmonary artery segments

muscle

muscle phenotype ( J:56948 )

N • unlike in Nos1 null mice, lower esophageal sphincter display normal electrical field stimulation (60 V, 5 Hz) induced relaxation and rebound contraction

increased vasoconstriction ( J:57624 )

• enhanced hypoxic pulmonary vasoconstriction

• treatment with bradykinin results in transient vasodilation followed by sustained vasoconstriction, while in wild-type mice vasodilation is maintained

abnormal vasodilation ( J:112419 )

• acetylcholine addition fails to induce any response in pulmonary artery segments, unlike in pulmonary artery segments from wild-type mice where it induces vasodilation

decreased vasodilation ( J:28778 )

• aortic rings show no relaxation to acetylcholine as in wild-type

nervous system

nervous system phenotype ( J:37956 )

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

increased susceptibility to neuronal excitotoxicity ( J:111644 )

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

decreased neurotransmitter release ( J:119052 )

• GABA release after NMDA stimulation is significantly attenuated in the cerebral cortex, striatum and hippocampus

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

abnormal neutrophil physiology ( J:55936 )

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

reproductive system

abnormal penile erection ( J:89704 )

♂ • the maximal increase in intracavernous pressure induced by papaverine is reduced by 75% compared to wild-type controls

abnormal ejaculation ( J:59686 )

♂ • homozygous males have a decreased latency to ejaculation and reduced number of mounts and intromissions required for ejaculation compared to wild-type males

cellular

increased susceptibility to neuronal excitotoxicity ( J:111644 )

• the size of striatal lesions induced by malonate are significantly increased 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

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

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)
essential hypertension		DOID:10825	OMIM:145500 OMIM:603918 OMIM:604329 OMIM:607329 OMIM:608742 OMIM:610261 OMIM:610262 OMIM:610948 OMIM:611014	J:28778