Mouse Genome Informatics
hm1
    Nos3tm1Unc/Nos3tm1Unc
B6.129P2-Nos3tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• kainic acid injection of hippocampi does not cause blood-brain barrier breakdown

nervous system
• kainic acid injection of hippocampi does not cause blood-brain barrier breakdown


Mouse Genome Informatics
hm2
    Nos3tm1Unc/Nos3tm1Unc
B6.129P2-Nos3tm1Unc/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 40% die within the first hour of birth
• 85% of mice die by P10 compared with 13% of wild-type mice

growth/size
• fetuses from E18 to term demonstrate slight growth retardation (J:98913)
• Intrauterine Growth Retardation demonstrated by ultrasonographic imaging showing differences in embryo and gestational vesicle measurements in both longitudinal and transversal curves from Days 5.5 to 14.5. (J:140819)

cardiovascular system
• after remnant kidney surgery, homozygotes exhibit a significantly greater decrease (50%) in endothelial cell density in the glomeruli and renal cortex relative to similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit a significantly greater endothelial cell loss than similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes develop intraluminal thrombi unlike similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes develop microaneurysms unlike similarly-treated wild-type controls
• abnormalities in pulmonary vascular development
• disorganization of the extracellular matrix structure in the lung vasculature
• capillaries of preterm mice remain deep within thickened septae, instead of aligning with the saccular epithelium, resulting in significantly fewer capillaries abutting saccular airspaces
• severe with focal alveolar edema
• impaired pulmonary angiogenesis
• occasionally exhibit misalignment of pulmonary veins, which are seen in anomalous locations adjacent to the lung pleura, running alongside arterial vessels and sharing a common adventitial sheath
• E19.5 lungs show dramatic decrease of arteriolar branches and regions of marked capillary hypoperfusion
• diastolic dimension is increased compared to in wild-type mice
• membranous and muscular ventricular defects in 6 of 10 mice compared with 1 of 10 atrial septal defects in wild-type mice
• in response to transverse aortic constriction (TAC)-induced pressure overload, wild-type hearts exhibit a progressive cardiac hypertrophy with significant dilatory remodeling whereas mutant hearts show more modest and concentric cardiac hypertrophy at 3 weeks, with minimal further progression
• at 9 weeks after TAC, mutant hearts develop significantly less intestitial fibrosis, myocyte hypertrophy, and fetal gene re-expression (B-natriuretic peptide and alpha-skeletal actin) relative wild-type hearts
• however, homozygotes show no significant differences in baseline heart weight or myocyte size relative to wild-type mice
• high incidence (5 of 12) bicuspid aortic valves, however do not exhibit aortic coarctation
• ventricular hypertrophy
• E16 lungs show scattered areas of parenchymal and interlobar hemorrhages
• at 9 weeks of TAC, wild-type hearts exhibit a rightward shift of LV pressure-volume (PV) loops and end-systolic and end-diastolic PV relations reflecting remodeling; in contrast, mutant hearts display a leftward shift with smaller end-diastolic and end-systolic chamber volumes, as well as preserved wall thickness and fractional shortening, indicating preserved or enhanced systolic and diastolic function
• in fetal atrioventricular endothelial cushions, septum primum and right and left ventricular myocardium
• at E12.5, E15.5 and P1 in the myocardium
• in response to TAC-induced pressure overload, homozygotes exhibit a similar or greater rise in LV systolic pressure and ventricular afterload (arterial elastance [Ea]) at 9 weeks relative to wild-type mice
• at 2 months after right subcapsular nephrectomy and surgical resection of the poles of the left kidney to produce a remnant kidney (RK) model, homozygotes fail to exhibit a further increase in systolic blood pressure relative to sham-operated homozygotes, unlike wild-type controls

respiratory system
• E16 lungs show scattered areas of parenchymal and interlobar hemorrhages
• fetal lungs demonstrate abnormally compact lung structure and lungs of pups show evidence of septal thickening and reduced airspaces
• E20 lungs display absence of discernible basement membrane in the distal airways
• exhibit a decrease in apoptosis in the lungs
• E16 lungs display scattered subpleural hematomas
• abnormalities in pulmonary vascular development
• disorganization of the extracellular matrix structure in the lung vasculature
• capillaries of preterm mice remain deep within thickened septae, instead of aligning with the saccular epithelium, resulting in significantly fewer capillaries abutting saccular airspaces
• severe with focal alveolar edema
• observe an increase in markedly swollen glycogen laden pneumocytes protruding into airspaces compared to wild-type
• no evidence of lamellar bodies in type II pneumocytes
• pups exhibit marked septal thickening
• some newborns exhibit severe respiratory distress
• lack of surfactant in bronchial alveolar lavage fluid

homeostasis/metabolism
• after remnant kidney surgery, homozygotes develop intraluminal thrombi unlike similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in BUN levels relative to similarly-treated wild-type controls
• serum osteocalcin (BGLAP) levels are significantly higher in sham treated compared to wild-type sham mice at baseline, 14 weeks and remained higher
• serum TRAP5b (ACP5) concentrations are significantly higher in sham treated compared wild-type sham treated mice at all time points
• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in serum creatinine levels relative to similarly-treated wild-type controls
• some newborns show varying levels of cyanosis
• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in urinary albumin excretion relative to similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit a 46% increase in glomerular collagen IV deposition relative to similarly-treated wild-type controls
• thin strands of connective tissue distributed loosely within the interglomerular interstitium (J:117046)
• after remnant kidney surgery, homozygotes exhibit a 38% increase in collagen III deposition in the tubulointerstitium relative to similarly-treated wild-type controls (J:148626)

muscle
• at 9 weeks of TAC, wild-type hearts exhibit a rightward shift of LV pressure-volume (PV) loops and end-systolic and end-diastolic PV relations reflecting remodeling; in contrast, mutant hearts display a leftward shift with smaller end-diastolic and end-systolic chamber volumes, as well as preserved wall thickness and fractional shortening, indicating preserved or enhanced systolic and diastolic function

cellular
• in fetal atrioventricular endothelial cushions, septum primum and right and left ventricular myocardium
• at E12.5, E15.5 and P1 in the myocardium
• at 2 months after right subcapsular nephrectomy and surgical resection of the poles of the left kidney to produce a remnant kidney (RK) model, homozygotes exhibit a 4.6-fold increase in peritubular endothelial cell apoptosis relative to similarly-treated wild-type controls
• in two week old mice based upon TUNEL staining and the presence of Apoptotic nuclei with a dense punctate appearance
• after remnant kidney surgery, homozygotes exhibit a 36% reduction of proliferating endothelial cells in cortical peritubular capillaries relative to similarly-treated wild-type controls
• in response to TAC-induced pressure overload, homozygotes (but not wild-type mice) exhibit blunted myocardial ROS generation and blunted nitrotyrosine, and gelatinase zymogen activity with no significant decline in the GSH/GSSH or NADPH/NADP ratio

endocrine/exocrine glands
• on day 0.5 of estrous cycle, mutant ovaries display a scarce number of ovulation sites and a higher number of anovulatory and luteinized unruptured follicles relative to wild-type controls (J:145649)
• on day 0.5 of estrous cycle, mutant ovaries exhibit significantly less corpora lutea than wild-type ovaries (9.7 +/- 1.2 versus 14.2 +/- 1.2, respectively) (J:145649)
• on day 0.5 of estrous cycle, mutant ovaries are significantly smaller than wild-type (J:145649)

reproductive system
• on day 0.5 of estrous cycle, mutant ovaries display a scarce number of ovulation sites and a higher number of anovulatory and luteinized unruptured follicles relative to wild-type controls (J:145649)
• on day 0.5 of estrous cycle, mutant ovaries exhibit significantly less corpora lutea than wild-type ovaries (9.7 +/- 1.2 versus 14.2 +/- 1.2, respectively) (J:145649)
• on day 0.5 of estrous cycle, mutant ovaries are significantly smaller than wild-type (J:145649)
• female homozygotes display a higher rate of anovulation than wild-type controls (48.3 +/- 7.3% versus 29.7 +/- 6.3, respectively) (J:145649)
• female homozygotes display a lower ovulation rate than wild-type controls (9.7 +/- 1.2% versus 14.2 +/- 1.2%, respectively) (J:145649)
• mutant dams show a higher incidence of embryo losses than wild-type dams (62.5% versus 16.7%, respectively) (J:145649)
• the mean rate of embryo losses detected in mutant dams is 49.90.1% versus less than 20% in wild-type dams (J:145649)
• in mutant dams, the highest %s of embryo losses occur between days 8.5 and 10.5 (55.6%) and at day 13.5 postcoitum (44.4% of total losses), whereas in control dams embryo losses occur at days 10.5 and 11.5 postcoitum (J:145649)
• on days 6.5 and 8.5 of pregnancy, the average number of embryos reaching implantation is lower in mutant mice relative to wild-type mice (4.0 +/- 0.4 versus 7.5 +/- 0.4, respectively) (J:145649)
• on day 0.5 of estrous cycle, female homozygotes show a significant reduction in the total number of recovered embryos (oocytes/zygotes) relative to wild-type controls (4.0 +/- 1.1 versus 10.4 +/- 1.6, respectively)
• thereafter, a mean of 2.0 +/- 1.0 of these recovered embryos are found to be fertilized, representing a non-fertilization rate of 50.7% versus only 3.3% in control littermates

immune system
• serum concentrations of TRAP5b (ACP5) are significantly higher in sham treated compared to wild-type sham treated mice at all time points
• fever in response to turpentine injection is enhanced compared to wild-type controls
• unlike in mice null for either Nos1 or Nos2, fever in response to LPS injection is not significantly different from wild-type controls
• after remnant kidney surgery, homozygotes exhibit increased macrophage infiltration in the glomeruli (15.4-fold) and in the tubulointerstitium (2.7-fold) relative to similarly-treated wild-type controls
• however, a similar increase in glomerular T-cell infiltration (62%) is seen in both RK groups

renal/urinary system
• at 2 months after right subcapsular nephrectomy and surgical resection of the poles of the left kidney to produce a remnant kidney (RK) model, homozygotes exhibit a 4.6-fold increase in peritubular endothelial cell apoptosis relative to similarly-treated wild-type controls
• in two week old mice based upon TUNEL staining and the presence of Apoptotic nuclei with a dense punctate appearance
• after remnant kidney surgery, homozygotes exhibit a 36% reduction of proliferating endothelial cells in cortical peritubular capillaries relative to similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in urinary albumin excretion relative to similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit increased macrophage infiltration in the glomeruli (15.4-fold) and in the tubulointerstitium (2.7-fold) relative to similarly-treated wild-type controls
• however, a similar increase in glomerular T-cell infiltration (62%) is seen in both RK groups
• in 80% of adult freshly isolated kidneys indentations are observed, indicating zones of parenchymal scarring
• 4% of glomeruli outside scarred area exhibit loss of cellularity and vasculature, a hyalinization like appearance
• after remnant kidney surgery, homozygotes develop microaneurysms unlike similarly-treated wild-type controls
• thin strands of connective tissue distributed loosely within the interglomerular interstitium (J:117046)
• after remnant kidney surgery, homozygotes exhibit a 38% increase in collagen III deposition in the tubulointerstitium relative to similarly-treated wild-type controls (J:148626)
• after remnant kidney surgery, homozygotes exhibit a 44% increase in tubulointerstitial injury relative to similarly-treated wild-type controls
• glomeruli within scarred areas are considerably smaller than wild-type
• after remnant kidney surgery, homozygotes exhibit a significantly greater endothelial cell loss than similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes develop intraluminal thrombi unlike similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit a 46% increase in glomerular collagen IV deposition relative to similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit increased mesangial proliferation relative to similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit increased matrix deposition in some glomeruli unlike similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes develop mesangiolysis unlike similarly-treated wild-type controls
• within scarred areas (J:117046)
• after remnant kidney surgery, homozygotes develop significant glomerulosclerosis, unlike similarly-treated wild-type controls (J:148626)
• after remnant kidney surgery, homozygotes develop significantly greater glomerular hypertrophy than similarly-treated wild-type controls
• frequently a large lipid droplet is observed with Bowman's capsule and the adjacent matrix
• after remnant kidney surgery, homozygotes exhibit more severe sloughing , vacuolization and nuclear exfoliation of tubular epithelial cells relative to similarly-treated wild-type controls
• within scarred areas
• the glomeruli often display no clear connection to typical large-diameter proximal tubules
• after remnant kidney surgery, homozygotes exhibit more severe tubular dilatation than similarly-treated wild-type controls
• after remnant kidney surgery, homozygotes exhibit more severe tubular cast formation than similarly-treated wild-type controls
• degeneration of the glomerular core components is common within the scarred zones
• in 2 week old mice, as pyknotic nuclei and vacuolated cytoplasm are observed
• after remnant kidney surgery, homozygotes exhibit significantly worse renal function relative to similarly-treated wild-type controls

skeleton
• serum concentrations of TRAP5b (ACP5) are significantly higher in sham treated compared to wild-type sham treated mice at all time points
• exagerated BMD decrease in ovariectomized mice
• between 10-20 weeks post sham-operation compared to sham-operated wild-type
• significantly greater cortical thickness in sham operated mice compared to sham operated wild-type mice
• serum osteocalcin (BGLAP) levels are significantly higher in sham compared wit wild-type sham mice at baseline and at 14 wk and remained higher

hematopoietic system
• serum concentrations of TRAP5b (ACP5) are significantly higher in sham treated compared to wild-type sham treated mice at all time points


Mouse Genome Informatics
hm3
    Nos3tm1Unc/Nos3tm1Unc
BKS.129P2-Nos3tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• moderate albuminuria is observed at 26 weeks of age

homeostasis/metabolism
• moderate albuminuria is observed at 26 weeks of age

cardiovascular system
• observed by 24 to 28 weeks of age


Mouse Genome Informatics
hm4
    Nos3tm1Unc/Nos3tm1Unc
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% of males die by 21 months of age, however female survival is similar to wild-type

growth/size
• both males and females weight less than wild-type at 21 months of age

cardiovascular system
• at 21 months of age, males exhibit wall thinning of the heart while females display an increase in wall thickness of the heart
• females, but not males, exhibit a significant increase in diastolic septal wall thickness and to a lesser degree in the posterior wall
• males exhibit a decrease in interventricular septum thickening at 21 months of age
• large increase in heart weight and heart weight to body weight ratio in males at 21 months of age and a smaller increase in females
• at 21 months of age, males have a large increase and females have a slight increase in heart size
• left-ventricular end-systolic chamber dilation (LVESD) is increased about 45% in homozygous males compared to 25% in wild-type males at 21 months of age; no differences seen in females
• left ventricular mass (LVMASS) is increased in both males and females at 21 months of age
• ratio between LVMASS and LV volume is increased in 21 month old males
• males at 21 months of age, but not at 5.5 months, exhibit a decrease in left ventricular posterior wall
• insulin stimulation of muscle blood flow is about 40% smaller than in wild-type
• males, but not females, exhibit a marked decrease in ejection fraction and shortening fraction at 21 months of age
• heart rate is increased in males at 5.5 months of age but not at 21 months of age
• heart rate is normal in females at 5.5 months of age but remains elevated at 21 months of age and does not fall with age as in wild-type
• mean blood pressure is significantly elevated in both males and females at 5.5 months of age
• at 21 months of age, females, but not males, continue to exhibit increased mean blood pressure
• females are hypertensive at 7 months of age and maintain the elevated pressure at 21 months of age, however do not exhibit any contractile dysfunction (J:102136)
• arterial hypertension (J:103153)
• elevated at 5.5 months of age in both males and females
• at 21 months of age, females, but not males, continue to exhibit an increased diastolic blood pressure
• elevated at 5.5 months of age in both males and females
• at 21 months of age, females, but not males, continue to exhibit an increased systolic blood pressure

homeostasis/metabolism
• plasma nitrite and nitrate concentrations are about 60% lower than in wild-type, indicating a defect of vascular NO production
• insulin-resistant homozygotes have 50% higher plasma levels of cholesterol
• insulin-resistant homozygotes have a 2-fold elevation of free fatty acid
• insulin-resistant homozygotes have a 2-fold elevation of triglycerides
• glucose infusion rate, glucose turnover rate, and glucose clearance rate are 30-40% lower during a hyperinsulinemic euglycemic clamp study
• basal and insulin-stimulated glucose transport in isolated skeletal muscle is about 40% lower than in wild-type
• fasting plasma insulin concentration is elevated almost 2-fold
• fasting hyperinsulinemia and glucose infusion rates during euglycemic clamp studies are 40% lower than in wild-type

muscle
• insulin stimulation of muscle blood flow is about 40% smaller than in wild-type
• males, but not females, exhibit a marked decrease in ejection fraction and shortening fraction at 21 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Hypertension, Essential 145500 J:103153


Mouse Genome Informatics
hm5
    Nos3tm1Unc/Nos3tm1Unc
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• after injection of platelet-activating factor (PAF), less than 10% mortality occurs within 30 minutes
• pretreatment with wortmannin before PAF treatment confers 100% protection to mutants and wild-type
• in BSA-induced anaphylaxis, all mutants survive compared to fatality in 82% of controls; in OVA model, 92% of control mice die but all mutants survive challenge

growth/size
• body weights at 14 weeks of age are approximately 7.5% lower than in wild-type (J:36559)
• body weight is signifcantly lower than controls at 14 days of age (J:101254)

homeostasis/metabolism
• plasma renin concentrations are nearly twice as high as in wild-type
• challenge with BSA 2 weeks after sensitization with BSA induces severe hypothermia and mice succumb to systemic shock reaction; mutants show no mortality and only a delayed, mild, transient hypothermia
• similar results are seen with OVA-induced anaphylaxis

cardiovascular system
• larger than in controls but only at 14 day
• medial wall area is greater than in controls in the fetus
• muscularity decreases after birth
• muscularity is reduced in the male but still greater than controls
• muscularity in females is like controls by 14 days of age
• right ventricle/body weight ratio increased in males
• right ventricle/left ventricle+septum ratio increased in males
• in BSA/BSA model of anaphylaxis, vascular permeability increased significantly in wild-type but very little in mutants; vascular leakage (extravasation) of Evans Blue dye (EB) is 2-fold lower than in wild-type mice
• in OVA/OVA model, no vascular permeability increase occurs in mutants and extravasation is significantly lower than in wild-type
• mean right ventricular pressure is elevated in males but not in females
• 670 beats per min vs. 709 beats per min in wild-type
• elevated in males but not in females

immune system
N
• exhibit a similar susceptibility to lipopolysaccharide-induced death as wild-type (J:36559)


Mouse Genome Informatics
hm6
    Nos3tm1Unc/Nos3tm1Unc
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• aortic rings isolated from homozygous mutant mice exhibit a significantly enhanced vasoconstriction in response to phenylephrine and a modestly enhanced vasoconstriction in response to serotonin
• aortic rings isolated from homozygous mutant mice show complete loss of endothelium-dependent vasorelaxation induced by acetylcholine and the calcium ionophore A23187
• in contrast, vasorelaxations to the endothelium-independent vasodilator nitroglycerin are enhanced resulting in a shift of EC50 by ~7-fold relative to wild-type values
• homozygotes display mild bradycardia relative to wild-type mice (J:54772)
• notably, chronic treatment of homozygotes with L-NAME induces a significant decrease of heart rate in both wild-type mice and mutant mice (J:54772)
• increase in blood pressure by about 18 mmHg
• homozygotes exhibit modest hypertension relative to wild-type mice
• chronic treatment of homozygotes with NOS inhibitor L-NAME fails to further increase blood pressure; in contrast, chronic L-NAME treatment increases blood pressure in wild-type (C57BL/6J) mice to a level similar to that noted in mutant mice

growth/size
• body weight is approximately 7.5% lower than wild-type at 14 weeks of age

homeostasis/metabolism
N
• unlike mice null for Nos1 or Nos2, no abnormalities in urine pH or bicarbonate concentrations are detected (J:64896)
• plasma renin is nearly 2x that of wild-type

muscle
• aortic rings isolated from homozygous mutant mice exhibit a significantly enhanced vasoconstriction in response to phenylephrine and a modestly enhanced vasoconstriction in response to serotonin
• aortic rings isolated from homozygous mutant mice show complete loss of endothelium-dependent vasorelaxation induced by acetylcholine and the calcium ionophore A23187
• in contrast, vasorelaxations to the endothelium-independent vasodilator nitroglycerin are enhanced resulting in a shift of EC50 by ~7-fold relative to wild-type values


Mouse Genome Informatics
ht7
    Nos3tm1Unc/Nos3+
B6.129P2-Nos3tm1Unc/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 38% of mice die by P10 compared with 13% of wild-type mice


Mouse Genome Informatics
ht8
    Nos3tm1Unc/Nos3+
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• aortic rings isolated from normotensive heterozygous mutant mice show normal endothelium-dependent vasorelaxation induced by acetylcholine and the calcium ionophore A23187
• however, vasorelaxations to the endothelium-independent vasodilator nitroglycerin are modestly enhanced in heterozygous aortic rings relative to wild-type

muscle
• aortic rings isolated from normotensive heterozygous mutant mice show normal endothelium-dependent vasorelaxation induced by acetylcholine and the calcium ionophore A23187
• however, vasorelaxations to the endothelium-independent vasodilator nitroglycerin are modestly enhanced in heterozygous aortic rings relative to wild-type


Mouse Genome Informatics
cx9
    Apoetm1Unc/Apoetm1Unc
Nos3tm1Unc/Nos3tm1Unc

B6.129P2-Nos3tm1Unc Apoetm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• microaneurysmal dilations in 20% of males
• sometimes involving coronary arteries
• plaques larger at 4 months than in Apoe homozygotes, by 182% for males and 165% for females
• plaques in descending aorta in 90% of males as opposed to 20% of Apoe males
• about 20mm higher than in Apoe homozygotes

renal/urinary system
• 15% of glomeruli with large lipid deposits in foam cells filling the glomeruli
• glomerular injury progresses to dystrophic calcification and glomerular loss
• 15% lower than in Apoe homozygotes

homeostasis/metabolism
• 66% higher than controls


Mouse Genome Informatics
cx10
    Nos2tm1Lau/Nos2tm1Lau
Nos3tm1Unc/Nos3tm1Unc

B6.129P2-Nos3tm1Unc Nos2tm1Lau
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected double homozygotes are born, no time of lethality provided


Mouse Genome Informatics
cx11
    Leprdb/Leprdb
Nos3tm1Unc/Nos3tm1Unc

BKS.Cg-Leprdb Nos3tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• albumin/creatinine ratio (ACR) is significantly higher than all controls
• glomerular basement membrane is markedly thickened by 16 weeks in comparison to all controls
• glomerular injury is significantly increased by 24-26 weeks in comparison to all controls
• substantial fibronectin accumulation is observed in glomeruli
• marked mesangial expansion is observed at 26 weeks of age
• marked mesangiolysis is observed at 26 weeks of age
• focal nodular sclerosis is observed at 26 weeks of age
• GFR is decreased in comparison to homozygous Nos3tm1Unc and Leprdb controls

homeostasis/metabolism
• at 26 weeks, serum creatinine is significantly higher than all controls
• hyperglycemia is first observed between 6-8 weeks of age, but is not higher than homozygous Leprdb control
• albumin/creatinine ratio (ACR) is significantly higher than all controls
• substantial fibronectin accumulation is observed in glomeruli

growth/size
• at 26 weeks, body weight is double that of lean and Nos3tm1Unc controls

cardiovascular system
• hypertension is observed between 24-28 weeks of age, but is not significantly higher than homozygous Nos3tm1Unc controls


Mouse Genome Informatics
cx12
    Nos1tm1Plh/Nos1tm1Plh
Nos3tm1Unc/Nos3tm1Unc

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected double homozygotes are born, no time of lethality provided