Mouse Genome Informatics
cx
    Nos1tm1Plh/Nos1tm1Plh
Nos2tm1Mrl/Nos2tm1Mrl
Nos3tm1Plh/Nos3tm1Plh

involves: 129S4/SvJae * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Renal tubular apoptosis, regeneration, glomerulosclerosis and glomerular thrombus formation in Nos1tm1Plh/Nos1tm1Plh Nos2tm1Mrl/Nos2tm1Mrl Nos3tm1Plh/Nos3tm1Plh mice

mortality/aging
• only 3 of 13 mutants survive to 10 months of age
• only 3 of 13 mutants survive to 10 months of age

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

cardiovascular system
• all mutants that die show wall thickening, perivascular fibrosis, and adventitial mast cell infiltration of the coronary arteries
• glomerular thrombus formation
• 2 mutants that die within 10 months of age, have pulmonary and liver congestion
• in 2 mutants that die within 10 months of age
• in 2 mutants that die within 10 months of age
• 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
• hypertension is similar to single Nos3 homozygotes, double Nos1/Nos3 homozygotes, and double Nos2/Nos3 homozygotes
• systolic blood pressure is significantly higher in mutants than wild-type under conscious conditions
• the two mutants with pulmonary and liver congestion and acute renal tubular necrosis exhibit acute circulatory failure

homeostasis/metabolism
• glomerular thrombus formation
• plasma concentrations of creatinine tend to be higher
• plasma osmolality is increased
• plasma concentrations of urea nitrogen are higher
• serum concentration is increased
• mutants exhibit only 2.4% and 3.6% of normal plasma and urinary NO levels, respectively
• renal prostacyclin levels are significantly higher in 1 week old mutants than in wild-type

renal/urinary system
• glomerular thrombus formation
• renal tubular lesions are seen predominantly in distal and collecting tubules than in proximal tubules
• glomerular thrombus formation
• 2 mutants that die within 10 months of age have acute renal tubular necrosis
• renal responsiveness to the anti-diuretic hormone, vasopressin, is reduced compared to wild-type, although central vasopressin release in unchanged
• impaired renal cAMP production
• hypotonic polyuria

behavior/neurological

digestive/alimentary system
• pyloric sphincter hypertrophy
• 3 of 5 mutants show enlargement of the stomach

liver/biliary system
• in 2 mutants that die within 10 months of age

respiratory system
• in 2 mutants that die within 10 months of age

skeleton
• at all time points
• increases slightly at 12 weeks of age
• trabecular bone in the proximal tibia is increased
• increased osteoclast function
• higher in females than in males
• bone formation rate and mineral apposition rate are increased
• higher in females than in males

hematopoietic system
• increased osteoclast function
• higher in females than in males

immune system
• increased osteoclast function
• higher in females than in males

muscle
• pyloric sphincter hypertrophy

cellular

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Insipidus, Nephrogenic, Autosomal 125800 J:100308