Phenotypes associated with this allele

• Allele Symbol: Nos2^tm1Mrl
• Allele Name: targeted mutation 1, Merck Research Laboratory
• Allele ID: MGI:2158791
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nos2^tm1Mrl/Nos2^tm1Mrl	B6.129S7-Nos2^tm1Mrl	MGI:4837857
hm2	Nos2^tm1Mrl/Nos2^tm1Mrl	either: 129S/Sv or B6J.129S7-Nos2^tm1Mrl	MGI:3041148
hm3	Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S7/SvEvBrd	MGI:2672127
hm4	Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S7/SvEvBrd * C57BL/6	MGI:3041147
hm5	Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S7/SvEvBrd * PL/J	MGI:4837858
cx6	Apoe^tm1Unc/Apoe^tm1Unc Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:4837860
cx7	Apc^Min/Apc^+ Msh2^tm1Mak/Msh2^tm1Mak Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:5636670
cx8	Apc^Min/Apc^+ Msh2^tm1Mak/Msh2^+ Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:5636667
cx9	Nos2^tm1Mrl/Nos2^tm1Mrl Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3789203
cx10	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3789190
cx11	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3789201
cx12	Nos1^tm1Plh/Nos1^tm1Plh Nos2^tm1Mrl/Nos2^tm1Mrl Nos3^tm1Plh/Nos3^tm1Plh	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6	MGI:4837924
cx13	Nos2^tm1Mrl/Nos2^tm1Mrl Tg(Myh6-Tnf)1.6Amf/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB	MGI:4837862
cx14	Fas^lpr/Fas^lpr Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S7/SvEvBrd * MRL	MGI:4837859

Genotype
MGI:4837857

hm1

• Allelic Composition: Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: B6.129S7-Nos2^tm1Mrl

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

skeleton

abnormal tooth hard tissue morphology ( J:98070 )

• distance between cementoenamel junction and alveolar bone crest is greater than for controls from 6 weeks on (without any bacterial challenge)

abnormal osteoclast morphology ( J:98070 )

abnormal osteoclast differentiation ( J:98070 )

• in vitro differentiation is markedly attenuated

decreased osteoclast cell number ( J:98070 )

• decreased by 25%

increased bone mineral density of femur ( J:98070 )

• bone mineral density of the femur is elevated at both 4 and 9 weeks of age

increased bone volume ( J:98070 )

• total bone volume is increased

increased compact bone mass ( J:98070 )

• increased cortical bone mass

• trabecular bone thickness and connectivity unchanged from controls

decreased bone resorption ( J:98070 )

• resorption activity is considerably decreased

craniofacial

abnormal tooth hard tissue morphology ( J:98070 )

• distance between cementoenamel junction and alveolar bone crest is greater than for controls from 6 weeks on (without any bacterial challenge)

immune system

abnormal osteoclast morphology ( J:98070 )

abnormal osteoclast differentiation ( J:98070 )

• in vitro differentiation is markedly attenuated

decreased osteoclast cell number ( J:98070 )

• decreased by 25%

abnormal response to infection ( J:98070 )

• do not respond to oral infection with Porphyromas gingivalis by bone loss

• serum levels of specific IgG are comparable to controls

homeostasis/metabolism

increased circulating prolactin level ( J:162957 )

• slightly elevated relative to controls

hematopoietic system

abnormal osteoclast morphology ( J:98070 )

abnormal osteoclast differentiation ( J:98070 )

• in vitro differentiation is markedly attenuated

decreased osteoclast cell number ( J:98070 )

• decreased by 25%

endocrine/exocrine glands

abnormal involution of the mammary gland ( J:162957 )

♀ • mammary gland regression after removal of pups is delayed

♀ • degree of regression at 72 hours is similar to controls

♀ • mammary gland development is normal at 10 days into lactation

abnormal mammary gland physiology ( J:162957 )

♀ • increase in apoptosis levels of involuting mammary glands is delayed

hyperlactation ( J:162957 )

♀ • elevated milk production

♀ • pups nourished by mutant mothers weigh more than pups nourished by control mothers

integument

abnormal involution of the mammary gland ( J:162957 )

♀ • mammary gland regression after removal of pups is delayed

♀ • degree of regression at 72 hours is similar to controls

♀ • mammary gland development is normal at 10 days into lactation

abnormal mammary gland physiology ( J:162957 )

♀ • increase in apoptosis levels of involuting mammary glands is delayed

hyperlactation ( J:162957 )

♀ • elevated milk production

♀ • pups nourished by mutant mothers weigh more than pups nourished by control mothers

cellular

abnormal osteoclast differentiation ( J:98070 )

• in vitro differentiation is markedly attenuated

growth/size/body

abnormal tooth hard tissue morphology ( J:98070 )

• distance between cementoenamel junction and alveolar bone crest is greater than for controls from 6 weeks on (without any bacterial challenge)

Genotype
MGI:3041148

hm2

• Allelic Composition: Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: either: 129S/Sv or B6J.129S7-Nos2^tm1Mrl

reproductive system

reproductive system phenotype ( J:73964 )

N • no difference in the number of oocytes released or survival of in vitro fertilized embryos is seen between female mutants and wild-type mice unlike in Nos3^tm1Weo female mutants

Genotype
MGI:2672127

hm3

• Allelic Composition: Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129S7/SvEvBrd

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

growth/size/body

increased body weight ( J:123048 )

• body weight is about 15% greater than controls

immune system

abnormal eosinophil cell number ( J:51635 )

• blood eosinophil numbers increase much less in OVA treated mice than in OVA treated controls

decreased eosinophil cell number ( J:51635 )

• numbers of eosinophils in bronchoalveolar lavage fluid half of control numbers in OVA treated mice

abnormal immune system physiology ( J:51635 )

increased IgG2a level ( J:51635 )

abnormal macrophage physiology ( J:120499 )

• PGE2 production increase in response to stimulation with IFNgamma and LPS is considerably more modest than for controls

increased interferon-gamma secretion ( J:51635 )

• higher IFN gamma secretion by lung and splenic T cells

decreased susceptibility to endotoxin shock ( J:25511 )

• anesthetized mutants are substantially protected from septic shock induced by endotoxic lipopolysaccharide (LPS), however unanesthetized mutants exhibit as much LPS-induced liver damage as wild-type mice

increased inflammatory response ( J:51635 )

• non-eosinophilic inflammatory responses are somewhat enhanced

increased susceptibility to bacterial infection ( J:25511 )

• mutants succumb to lower doses of Listeria monocytogenes than wild-type mice, with approximate 100-fold greater bacterial burdens in liver and spleen

cardiovascular system

cardiovascular system phenotype ( J:57624 )

N • unlike in mice null for Nos3 no significant abnormalities in hypoxic pulmonary vasoconstriction or vasodilation in response to bradykinin are detected

abnormal induced retina neovascularization ( J:112024 )

• more vascularization of the retinal surface than seen in controls after 5 days of oxygen exposure followed by 120 hours of hypoxia

abnormal heart right ventricle pressure ( J:57624 )

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

homeostasis/metabolism

abnormal homeostasis ( J:51635 )

• reactive nitrogen intermediates do not increase in OVA treated mice as they do in OVA treated controls

abnormal platelet aggregation ( J:120499 )

• significantly increased amounts of PxP2 are derived from platelet aggregation

decreased urine prostaglandin level ( J:120499 )

• considerably reduced amounts of PGE2 are excreted in urine

• also considerably reduced amounts of PGF2-like F2-isoprostanes excreted

abnormal bone healing ( J:123048 )

• callus cross-sectional area increased relative to controls during healing of fractured femora

• increased torsional failure during healing

delayed wound healing ( J:46763 )

• wound closure is significantly delayed

vision/eye

abnormal induced retina neovascularization ( J:112024 )

• more vascularization of the retinal surface than seen in controls after 5 days of oxygen exposure followed by 120 hours of hypoxia

abnormal vitreous body morphology ( J:112024 )

• intravitreal neovascularization is considerably less than in controls after 5 days of oxygen exposure followed by 120 hours of hypoxia

skeleton

abnormal bone healing ( J:123048 )

• callus cross-sectional area increased relative to controls during healing of fractured femora

• increased torsional failure during healing

abnormal trabecular bone morphology ( J:150159 )

• bone volume/trabecular volume is increased

renal/urinary system

decreased urine prostaglandin level ( J:120499 )

• considerably reduced amounts of PGE2 are excreted in urine

• also considerably reduced amounts of PGF2-like F2-isoprostanes excreted

hematopoietic system

abnormal eosinophil cell number ( J:51635 )

• blood eosinophil numbers increase much less in OVA treated mice than in OVA treated controls

decreased eosinophil cell number ( J:51635 )

• numbers of eosinophils in bronchoalveolar lavage fluid half of control numbers in OVA treated mice

increased IgG2a level ( J:51635 )

abnormal macrophage physiology ( J:120499 )

• PGE2 production increase in response to stimulation with IFNgamma and LPS is considerably more modest than for controls

abnormal platelet aggregation ( J:120499 )

• significantly increased amounts of PxP2 are derived from platelet aggregation

Genotype
MGI:3041147

hm4

• Allelic Composition: Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal cardiovascular system morphology ( J:101254 )

abnormal uterine artery morphology ( J:78274 )

♀ • the large arteries of the uterus during pregnancy have thickened arterial walls and smaller lumina

atherosclerotic lesions ( J:97522 )

• found in about 35% of homozygotes

abnormal heart ventricle morphology ( J:101254 )

• total ventricle weights are greater than controls for males only

abnormal cardiovascular system physiology ( J:97522 )

abnormal blood circulation ( J:65562 )

• islet blood flow under basal conditions is increased

increased myocardial infarct size ( J:87980 )

• area of infarction is greater than for controls in non-diabetic mice after ischemia-reperfusion

• reperfusion injury is less in diabetic mice than in diabetic controls

increased systemic arterial blood pressure ( J:87980 )

increased mean systemic arterial blood pressure ( J:87980 )

• relative to controls

• streptozotocin induced diabetes for 8 days results in a more modest increase in blood pressure than in similar controls

increased systemic arterial systolic blood pressure ( J:97522 )

• slightly increased at 3 months of age but not later

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:65562 , J:72215 )

N • normal serum insulin (J:65562)

N • obese mice on a high fat diet have normal insulin levels (J:72215)

increased myocardial infarct size ( J:87980 )

• area of infarction is greater than for controls in non-diabetic mice after ischemia-reperfusion

• reperfusion injury is less in diabetic mice than in diabetic controls

abnormal blood homeostasis ( J:97522 )

increased circulating creatinine level ( J:97522 )

• slightly elevated levels

increased circulating cholesterol level ( J:97522 )

• levels 1.7 times normal at 9 months of age

increased circulating triglyceride level ( J:155090 )

• elevated plasma triglycerides

abnormal circulating serum albumin level ( J:97522 )

• slightly reduced at 3 months and tending to decline with age

abnormal glucose homeostasis ( J:65562 )

abnormal circulating glucose level ( J:65562 )

• resistant to hyperglycemia induced by multiple low doses of streptozotocin

improved glucose tolerance ( J:72215 )

• hyperglycemic in the first 30 minutes of a glucose tolerance test

• return to fasting glucose levels by 90 minutes when controls are still hyperglycemic

increased insulin sensitivity ( J:72215 )

abnormal hormone level ( J:109674 )

abnormal circulating estradiol level ( J:89542 )

• the cyclic changes in estradiol level are abnormal in homozygous mutant females with the peak in estradiol concentration coming later than in 129/SvEv wild-type females

decreased adiponectin level ( J:155090 )

abnormal adrenocorticotropin level ( J:109674 )

• plasma ACTH levels increase much more modestly after LPS treatment than for controls

increased renin activity ( J:155090 )

• plasma renin activity is increased

decreased cerebral infarct size ( J:44287 )

• volume of infarction 96 hours after middle cerebral artery occlusion is 28% smaller than controls

• volume of infarction is similar to controls 24 hours after cerebral artery occlusion

decreased susceptibility to kidney reperfusion injury ( J:57621 )

• protected from renal ischemia-reperfusion injury as indicated by lower serum creatine levels compared to controls

• less tubular necrosis, tubular structure is almost normal

• better survival rate at 24 hours after surgeries

reproductive system

abnormal uterus morphology ( J:78274 )

♀ • the lining of the uterus during pregnancy shows a distinct lack of cellularity in homozygous female mutants compared to wild-type females

prolonged diestrus ( J:89542 )

♀ • diestrus length is increased in homozygous mutant females compared to 129/SvEv wild-type mice without an increase in total oestrus cycle length

decreased litter size ( J:78274 )

• by mid-gestation homozygous female mutants have significantly fewer viable embryos compared to wild-type females

nervous system

nervous system phenotype ( J:104959 )

N • chronic nerve constriction does not lead to breakdown of small myelinated fibers

decreased cerebral infarct size ( J:44287 )

• volume of infarction 96 hours after middle cerebral artery occlusion is 28% smaller than controls

• volume of infarction is similar to controls 24 hours after cerebral artery occlusion

neuron degeneration ( J:104959 )

• moderate breakdown of larger caliber myelinated fibers 5 days after chronic nerve constriction at a time when controls have far fewer surviving fibers

• fiber numbers are declining at 14 days but at a slower rate than for controls

• degenerating myelinated fibers persist longer after nerve crush injury

abnormal peripheral nervous system regeneration ( J:104959 )

• no regenerative myelinated sprouts at 21 days when they have begun to appear in controls

• regenerating fibers are smaller in caliber after nerve crush injury

• similar to controls by 6 weeks after nerve crush injury

• nerve fiber regeneration is delayed and new fibers are smaller in diameter after nerve transection

delayed peripheral nervous system regeneration ( J:104959 )

• nerve fiber regeneration is delayed and new fibers are smaller in diameter after nerve transection

behavior/neurological

increased food intake ( J:72215 )

• consume 1.6 times as much food as controls on a high fat diet

abnormal motor capabilities/coordination/movement ( J:44287 )

• motor deficiencies improve between 24 and 96 hours after cerebral artery occlusion unlike controls

abnormal sensory capabilities/reflexes/nociception ( J:104959 )

abnormal response to tactile stimuli ( J:104959 )

• tactile hypersensitivity disappears between 5 and 14 days after the start of chronic nerve constriction while it persists through day 14 in controls

allodynia ( J:104959 )

• tactile allodynia observed at 3 weeks when neuropathic pain is diminishing in controls

abnormal thermal nociception ( J:104959 )

• thermal hypersensitivity disappears between 5 and 14 days after the start of chronic nerve constriction while it persists through day 14 in controls

• delayed thermal hypersensitivity observed at 3 weeks when neuropathic pain is diminishing in controls

immune system

pancreas inflammation ( J:65562 )

• low level of islet inflammation as compared to controls when treated with streptozotocin

• islet size is normal

increased length of allograft survival ( J:54764 )

• lower rejection rate of CBA/CaJ cardiac grafts

• lower levels of apoptosis by all measures used

renal/urinary system

decreased susceptibility to kidney reperfusion injury ( J:57621 )

• protected from renal ischemia-reperfusion injury as indicated by lower serum creatine levels compared to controls

• less tubular necrosis, tubular structure is almost normal

• better survival rate at 24 hours after surgeries

endocrine/exocrine glands

pancreas inflammation ( J:65562 )

• low level of islet inflammation as compared to controls when treated with streptozotocin

• islet size is normal

growth/size/body

increased body weight ( J:101254 )

• body weight is greater than controls for males only

increased growth rate ( J:72215 )

• experience greater weight gain on a high fat diet

digestive/alimentary system

abnormal digestion ( J:84264 )

• do not respond to gastric luminal acid with as great an increase in gastric blood flow as do controls

• vascular resistance is not diminished

decreased digestive secretion ( J:142280 )

• mucus accumulation rate about 25% of controls

• firmly adherent layer of mucus is thinner than in controls

liver/biliary system

liver fibrosis ( J:94156 )

• fibrotic changes in the livers of mice on a high fat diet particularly around degenerating hepatocytes and the central vein area

• collagen fraction is higher than in controls when on a high fat diet

Genotype
MGI:4837858

hm5

• Allelic Composition: Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129S7/SvEvBrd * PL/J

immune system

increased susceptibility to experimental autoimmune encephalomyelitis ( J:46192 )

• levels of experimental autoimmune encephalitis are significantly greater than controls starting 13 days after injection with myelin basic protein

• remission levels are much lower than for controls

Genotype
MGI:4837860

cx6

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:64566 )

N • no effect on plasma cholesterol, triglycderide, or nitrate levels when compared to Apoe^tm1Unc controls on any diet tested

decreased cholesterol level ( J:64566 )

• total cholesterol in the aorta is reduced 40% in males and 50% in females

• free cholesterol in the aorta is reduced 40% in males and 50% in females

• cholesterol ester in the aorta is reduced 57% in males and 72% in females

growth/size/body

increased body weight ( J:64566 )

• females are slightly heavier than controls

• no weight effect in males

cardiovascular system

atherosclerotic lesions ( J:64566 )

• lesions are smaller and flatter

• male lesions are 50% smaller

• female lesions are 30% smaller

Genotype
MGI:5636670

cx7

• Allelic Composition: Apc^Min/Apc⁺; Msh2^tm1Mak/Msh2^tm1Mak; Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

digestive/alimentary system

intestine polyps ( J:200824 )

• mutants exhibit similar polyp formation in the small intestine and colon as mice heterozygous for Apc^Min and homozygous for Msh2^tm1Mak

Genotype
MGI:5636667

cx8

• Allelic Composition: Apc^Min/Apc⁺; Msh2^tm1Mak/Msh2⁺; Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

digestive/alimentary system

intestine polyps ( J:200824 )

• mutants exhibit enhanced polyp number in the small intestine, but not in the colon compared to double Apc^Min Msh2^tm1Mak heterozygotes

Genotype
MGI:3789203

cx9

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

mortality/aging

decreased survivor rate ( J:100308 )

• 60-80% survival rate at 10 months of age

premature death ( J:100308 )

• about 20-40% die before 10 months of age

reproductive system

reduced fertility ( J:100308 )

• slight reduction in the number of offspring produced from breeding pairs

cardiovascular system

decreased heart rate ( J:100308 )

increased systemic arterial systolic blood pressure ( J:100308 )

homeostasis/metabolism

increased blood osmolality ( J:100308 )

• plasma osmolality is increased

increased blood urea nitrogen level ( J:100308 )

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

renal/urinary system

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

polyuria ( J:100308 )

behavior/neurological

polydipsia ( J:100308 )

Genotype
MGI:3789190

cx10

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

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

Genotype
MGI:3789201

cx11

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

mortality/aging

decreased survivor rate ( J:100308 )

• 60-80% survival rate at 10 months of age

premature death ( J:100308 )

• about 20-40% die before 10 months of age

reproductive system

reduced fertility ( J:100308 )

• slight reduction in the number of offspring produced from breeding pairs

homeostasis/metabolism

increased blood osmolality ( J:100308 )

• plasma osmolality is increased

increased blood urea nitrogen level ( J:100308 )

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

renal/urinary system

decreased urine sodium level ( J:100308 )

decreased urine osmolality ( J:100308 )

polyuria ( J:100308 )

behavior/neurological

polydipsia ( J:100308 )

Genotype
MGI:4837924

cx12

• Allelic Composition: Nos1^tm1Plh/Nos1^tm1Plh; Nos2^tm1Mrl/Nos2^tm1Mrl; Nos3^tm1Plh/Nos3^tm1Plh
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:155090 )

• 85% of males die within 11 months whereas only 35-40% of males of any double homozygous genotype die at that time point

cardiovascular system

abnormal cardiovascular system morphology ( J:155090 )

arteriosclerosis ( J:155090 )

• in most of the vasculature

• lipid accumulation in the aorta

perivascular fibrosis ( J:155090 )

• perivascular fibrosis of large epicardial coronary arteries and renal arteries

thick ventricular wall ( J:155090 )

• anterior and posterior ventricular walls are thickened

abnormal cardiovascular system physiology ( J:155090 )

hypertension ( J:155090 )

abnormal vascular endothelial cell physiology ( J:155090 )

• endothelium dependent relaxation lacking

abnormal vascular wound healing ( J:155090 )

• no vascular lesions in 2 month old males

• significant neointimal formation at 5 months

• medial thickening at 5 months

adipose tissue

increased white adipose tissue amount ( J:155090 )

• perirenal and epididymal white adipose weights are increased

homeostasis/metabolism

abnormal vascular wound healing ( J:155090 )

• no vascular lesions in 2 month old males

• significant neointimal formation at 5 months

• medial thickening at 5 months

abnormal circulating glucose level ( J:155090 )

• significantly increased after i.v. glucose

increased circulating LDL cholesterol level ( J:155090 )

increased circulating triglyceride level ( J:155090 )

• elevated plasma triglycerides

decreased adiponectin level ( J:155090 )

Genotype
MGI:4837862

cx13

• Allelic Composition: Nos2^tm1Mrl/Nos2^tm1Mrl; Tg(Myh6-Tnf)1.6Amf/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB

cardiovascular system

abnormal cardiac muscle contractility ( J:109732 )

• isoproterenol improved fractional shortening relative to transgenic mice with Nos2 intact

decreased cardiac muscle contractility ( J:109732 )

abnormal heart ventricle pressure ( J:109732 )

• isoproterenol improved left ventricular pressure development relative to transgenic mice with Nos2 intact

decreased heart rate ( J:109732 )

irregular heartbeat ( J:109732 )

abnormal atrioventricular node conduction ( J:109732 )

abnormal heart electrocardiography waveform feature ( J:109732 )

abnormal myocardial fiber physiology ( J:109732 )

muscle

abnormal cardiac muscle contractility ( J:109732 )

• isoproterenol improved fractional shortening relative to transgenic mice with Nos2 intact

decreased cardiac muscle contractility ( J:109732 )

Genotype
MGI:4837859

cx14

• Allelic Composition: Fas^lpr/Fas^lpr; Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129S7/SvEvBrd * MRL

renal/urinary system

abnormal urine homeostasis ( J:42666 )

• protein excretion less than controls at 20 weeks of age but not significantly

decreased urine nitrite level ( J:42666 )

• excrete very low levels of nitrite/nitrate relative to controls, heterozygotes are intermediate

• serum and urine levels of nitrite/nitrate are similar

homeostasis/metabolism

abnormal blood homeostasis ( J:42666 )

• serum and urine levels of nitrite/nitrate are similar

abnormal urine homeostasis ( J:42666 )

• protein excretion less than controls at 20 weeks of age but not significantly

decreased urine nitrite level ( J:42666 )

• excrete very low levels of nitrite/nitrate relative to controls, heterozygotes are intermediate

• serum and urine levels of nitrite/nitrate are similar

immune system

immune system phenotype ( J:42666 )

N • vasculitis absent in renal vessels, unlike controls

N • anti-DNA levels similar to controls

abnormal immunoglobulin level ( J:42666 )

• IgG1/IgG3 ratio is higher than controls

decreased IgG level ( J:42666 )

• significantly reduced rheumatoid factor specific IgG antibodies

decreased IgM level ( J:42666 )

• significantly reduced rheumatoid factor specific IgM antibodies

hematopoietic system

abnormal immunoglobulin level ( J:42666 )

• IgG1/IgG3 ratio is higher than controls

decreased IgG level ( J:42666 )

• significantly reduced rheumatoid factor specific IgG antibodies

decreased IgM level ( J:42666 )

• significantly reduced rheumatoid factor specific IgM antibodies