Phenotypes Associated with This Genotype

Genotype
MGI:3789190

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

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

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

renal tubular necrosis ( J:100308 )

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

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 )

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 )

renal tubular necrosis ( J:100308 )

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

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