Phenotypes Associated with This Genotype

Genotype
MGI:4366780

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

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

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