Mouse Genome Informatics
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    Nos3tm1Plh/Nos3tm1Plh
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• about 80% survival rate at 10 months of age
• about 20% die before 10 months of age

cardiovascular system
• decrease in lower thoracic aortic flow
• in isolated perfused hearts
• however, coronary flow per beat is not significantly different from controls
• total pulmonary resistance and pulmonary vascular resistance are increased
• acetylcholine fails to decrease total systemic resistance unlike in wild-type mice
• enhanced hypoxic pulmonary vasoconstriction
• treatment with bradykinin results in transient vasodilation followed by sustained vasoconstriction, while in wild-type mice vasodilation is maintained
• acetylcholine addition fails to induce any response in pulmonary artery segments, unlike in pulmonary artery segments from wild-type mice where it induces vasodilation
• aortic rings show no relaxation to acetylcholine as in wild-type
• increase in right ventricle systolic pressure in mice exposed to chronic mild hypoxia compared to similarly treated wild-type controls (J:57624)
• in isolated perfused hearts (J:60525)
• in isolated whole lungs baseline pulmonary perfusion pressure is increased compared to wild-type controls
• acetylcholine induced decrease in systemic arterial pressure is less than in wild-type controls

homeostasis/metabolism
• the size of striatal lesions induced by malonate are significantly increased compared to similarly treated controls
• insulin resistance in the liver and peripheral tissues
• 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
N
• unlike in Nos1 null mice, lower esophageal sphincter display normal electrical field stimulation (60 V, 5 Hz) induced relaxation and rebound contraction (J:56948)
• enhanced hypoxic pulmonary vasoconstriction
• treatment with bradykinin results in transient vasodilation followed by sustained vasoconstriction, while in wild-type mice vasodilation is maintained
• acetylcholine addition fails to induce any response in pulmonary artery segments, unlike in pulmonary artery segments from wild-type mice where it induces vasodilation
• aortic rings show no relaxation to acetylcholine as in wild-type

nervous system
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)
• the size of striatal lesions induced by malonate are significantly increased compared to similarly treated controls
• GABA release after NMDA stimulation is significantly attenuated in the cerebral cortex, striatum and hippocampus

immune system
• increase in baseline rolling
• treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice
• 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
• following thioglycollate injection neutrophil accumulation in the peritoneum is significantly enhanced compared to wild-type mice

reproductive system
• the maximal increase in intracavernous pressure induced by papaverine is reduced by 75% compared to wild-type controls (J:89704)
• homozygous males have a decreased latency to ejaculation and reduced number of mounts and intromissions required for ejaculation compared to wild-type males (J:59686)

cellular
• the size of striatal lesions induced by malonate are significantly increased compared to similarly treated controls
• increase in baseline rolling
• treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice
• 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

hematopoietic system
• increase in baseline rolling
• treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice
• 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
• following thioglycollate injection neutrophil accumulation in the peritoneum is significantly enhanced compared to wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Hypertension, Essential 145500 J:28778