Mouse Genome Informatics
hm1
    Nos2tm1Lau/Nos2tm1Lau
B6.129P2-Nos2tm1Lau
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• better survival after myocardial infarction than for wild-type controls (J:115413)
• increased sensitivity to ionizing radiation

cardiovascular system
N
• unlike mice null for Nos3, ischemia induced retinal neovascularization is not significantly different from controls (J:106207)
• choroidal neovascularization following laser-induced rupture of Bruch's membrane is reduced
• retinal revascularization after ischemia produces small highly branched blood vessels
• three fold more branching occurs in revascularization than occurs in controls
• increased hyalination and patchy loss of cross-striations when on 100% oxygen
• hypoxia causes less increase in the RV/LV+Septum ratio than is found in controls
• left ventricular maximum developed pressure was similar to sham operated animals 4 months after myocardial infarction rather than being reduced as in wild-type controls
• more significant drop in systolic blood pressure after myocardial infarction than is seen in controls

vision/eye
• choroidal neovascularization following laser-induced rupture of Bruch's membrane is reduced

nervous system
• shortened latency to seizures induced by kainic acid when on a normal diet
• behavior responses correspond to grade V seizures
• latency to seizure is prolonged when fed a ketogenic diet
• increased myelin pathology after treatment with cuprizone
• decreased numbers of mature oligodendrocytes after cuprizone treatment
• numbers of oligodendrocytes reduced to 50% of controls after 3.5 weeks
• undergo increased apoptosis which is not seen for microglia and astrocytes
• recover better from compression injury to the spinal cord than do controls, severity of behavioral deficit due to injury is somewhat less

digestive/alimentary system
• less susceptibility to dextran sodium sulfate induced colitis
• less severe weight loss, blood loss and macroscopic damage
• improved survival

homeostasis/metabolism
• shorter time to thrombus formation and vessel occlusion
• increased platelet deposition
• no effect on streptozotocin induced diabetis
• increased sensitivity to ionizing radiation
• recover better from compression injury to the spinal cord than do controls, severity of behavioral deficit due to injury is somewhat less

behavior/neurological
• shortened latency to seizures induced by kainic acid when on a normal diet
• behavior responses correspond to grade V seizures
• latency to seizure is prolonged when fed a ketogenic diet
• inhibitory effect of insulin on feeding is enhanced by 10 -8M TNF alpha
• significantly more time spent in REM sleep during the light period
• increased REM sleep results from more REM episodes and shortened periods in between
• more non REM sleep episodes in light period but of shorter duration
• significantly less non REM sleep during dark periods

respiratory system
N
• alveolar fluid clearance unaffected by amilorid and forskolin which both affect clearance in controls (J:71505)
• increased ulceration in 100% oxygen than seen with controls
• reduced lung injury relative to controls after 55 hours at 100% oxygen

immune system
• less susceptibility to dextran sodium sulfate induced colitis
• less severe weight loss, blood loss and macroscopic damage
• improved survival
• elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading

hematopoietic system
• elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading
• increased platelet deposition

skeleton
• less recovery of lost bone volume due to bone unloading 7 days after reloading
• elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading
• lower mineral aposition rate than in controls 7 days after bone reloading


Mouse Genome Informatics
hm2
    Nos2tm1Lau/Nos2tm1Lau
B6.129P2-Nos2tm1Lau/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• following infection with mycoplasma, the numbers of large surfactant aggregates is decreased and higher protein to lipid ratios are present in the bronchoalveolare lavage fluid compared to similarly infected wild-type mice
• following infection with mycoplasma, the minimal surface area on the pulsating bubble is increased and the levels of surfactant protein are decreased compared to similarly infected wild-type mice

behavior/neurological
• mice display a more pronounced diurnal variation of sleep-wake activity
• mice spend more time in REM sleep during the light phase as a result of an increased number of REM episodes and shortened duration of the inter REM intervals
• mice display a more pronounced diurnal variation of sleep-wake activity
• mice spend less time in non-REM sleep during the dark phase
• during the light phase mice spend the same amount of time in non-REM sleep but have a higher number of non-REM episodes of shorter average duration

nervous system
• during non-REM sleep the absolute value of slow wave activity is increased

immune system
• unlike in wild-type mice, LPS injection fails to reduce nighttime body temperature relative to saline injected controls
• fever in response to LPS injection is partially reduced compared to wild-type controls
• the fever response to LPS is initiated but not sustained
• however, fever in response to turpentine injection is not different from controls


Mouse Genome Informatics
hm3
    Nos2tm1Lau/Nos2tm1Lau
B6;129P2-Nos2tm1Lau/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• following hepatic ischemia and reperfusion compared with similarly treated wild-type mice
• following hepatic ischemia and reperfusion compared with similarly treated wild-type mice
• following hepatic ischemia and reperfusion, mice exhibit reduced liver injury with improved histology due to only mild signs of vascular changes, necrosis, and apoptosis and decreased serum alanine and aspartate transferase levels, and leukocyte (neutrophils, CD3 lymphocytes, CD4 T cells, and granulocytes) recruitment compared with similarly treated wild-type mice


Mouse Genome Informatics
hm4
    Nos2tm1Lau/Nos2tm1Lau
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• unlike in mice null for Nos1 or Nos3, no abnormalities in leukocyte rolling or adhesion are detected (J:55936)


Mouse Genome Informatics
hm5
    Nos2tm1Lau/Nos2tm1Lau
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
• reduced survival 8 days after 30 minutes of experimentally induced kidney eschemia relative to controls

cardiovascular system
N
• blood pressure and heart rate are normal (J:36559)
• blood pressure drops less in response to LPS injection than it does in controls

homeostasis/metabolism
N
• after injection of platelet-activating factor (PAF), >90% mortality occurs within 30 minutes, similar to wild-type controls (J:113106)
• pretreatment with wortmannin before PAF treatment confers 100% protection to mutants and wild-type (J:113106)
• higher plasma creatinine levels 24 hours after experimentally induced kidney eschemia than in controls
• elevation in plasma AVP due to LPS injection persists longer than controls, still significantly elevated after 6 hours whereas levels more moderately elevated in controls aftr 4 hours.
• plasma leptin concentrations are significantly reduced
• elevated tissue myeloperoxidase levels relative to controls 9 days after kidney eschemia
• hyperglycemic in the first 30 minutes of a glucose tolerance test
• return to fasting glucose levels by 90 minutes when controls are still hyperglycemic

immune system
N
• homozygotes are indistinguishable from wild-type in appearance, histology, growth rate, reproduction, and in mortality in an LPS-induced model of septic shock (J:29677)
• growth of Mycobacterium leprae unaffected (J:64036)
• normal development of Peyer's patches (J:80204)
• increased numbers of both CD4+ and CD8+ cells in inguinal lymph nodes
• increased cellularity of inguinal lymph nodes
• primary immune responses are unaffected
• increased T-cell proliferative response to protein antigens
• "clonal burst size" is unchanged
• greatly increased granulomatous inflammation when infected with Mycobacterium leprae
• resembles borderline tuberculoid lesions of leprosy
• intracellular growth of Mycobacterium tuberculosis and Francisella tularensis is increased but to highly variable extent

tumorigenesis
• increased rate of growth of ascites tumor cells
• no apoptosis in ascites tumor cells 2 weeks after innoculation
• growth of solid tumors from ascites tumor cells is prevented

adipose tissue
• reduced amounts of epididymal white adipose tissue

reproductive system
• significantly increased diameter and volume (J:84347)
• 31% increase (J:84347)
• numbers of pachytene spermatocytes and round spermatids are increased (J:84347)
• decreased apoptosis of pachytene, early round spermatids at stages I-IV, and diplotene dividing spermatocytes at stages XI-XII (J:84347)
• reduced heat induced apoptosis (J:84347)
• 65.5% increase in sperm content (J:84347)
• significantly higher numbers of 2-celled embryos produced when homozygotes are intercrossed
• blastocyst formation is similar to controls
• fertilization rate of mutant sperm and normal ova is significantly higher than controls
• fertilization rate of mutant ova and normal sperm is much higher than controls

endocrine/exocrine glands
• significantly increased diameter and volume (J:84347)
• 31% increase (J:84347)

hematopoietic system
• increased numbers of both CD4+ and CD8+ cells in inguinal lymph nodes
• increased T-cell proliferative response to protein antigens
• "clonal burst size" is unchanged

growth/size/body
• experience greater weight gain on a high fat diet

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

integument
• greatly increased granulomatous inflammation when infected with Mycobacterium leprae
• resembles borderline tuberculoid lesions of leprosy


Mouse Genome Informatics
hm6
    Nos2tm1Lau/Nos2tm1Lau
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• small but significant increase in urine pH and bicarbonate concentration

homeostasis/metabolism
• small but significant increase in urine pH and bicarbonate concentration


Mouse Genome Informatics
cx7
    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
cx8
    ApcMin/Apc+
Nos2tm1Lau/Nos2tm1Lau

B6.Cg-Nos2tm1Lau ApcMin
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• polyp size reduced
• 29% of tumor incidence observed in controls
• multiplicity of tumors reduced to about 9% of control level


Mouse Genome Informatics
cx9
    ApcMin/Apc+
Nos2tm1Lau/Nos2+

B6.Cg-Nos2tm1Lau ApcMin
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• polyp size reduced
• 68% of tumor incidence observed in controls
• multiplicity of tumors reduced to about 33% of control level


Mouse Genome Informatics
cx10
    Nos2tm1Lau/Nos2tm1Lau
Tg(MMTV-PyVT)634Mul/0

B6.Cg-Nos2tm1Lau Tg(MMTV-PyVT)634Mul
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• Background Sensitivity: moderate rate of growth of tumors after reaching 1 cubic cm relative to FVB mice
• Background Sensitivity: fewer tumors develop than in FVB mice
• slower to develop mammary tumors (J:84218)
• delayed tumor development relative to FVB mice (J:84218)
• Background Sensitivity: delay in palpable tumor development of 3-4 weeks relative to mice on a FVB background (J:121391)
• Background Sensitivity: latency to tumors of 92 days (J:121391)


Mouse Genome Informatics
cx11
    Nos2tm1Lau/Nos2tm1Lau
Tg(MMTV-PyVT)634Mul/0

FVB.Cg-Nos2tm1Lau Tg(MMTV-PyVT)634Mul
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• Background Sensitivity: exponential growth of tumors after reaching 1cubic cm
• Background Sensitivity: more tumors appear than in mice on a B6 background
• palpable tumor development is more rapid than in mice on a B6 background; latency to tumor appearance is ~53 days


Mouse Genome Informatics
cx12
    Adh5tm1Stam/Adh5tm1Stam
Nos2tm1Lau/Nos2tm1Lau

involves: 129 * 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal survival following diethylnitrosamine (DEN) challenged (J:173666)


Mouse Genome Informatics
cx13
    Nos1tm1Plh/Nos1tm1Plh
Nos2tm1Lau/Nos2tm1Lau

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


Mouse Genome Informatics
cx14
    Il10tm1Cgn/Il10tm1Cgn
Nos2tm1Lau/Nos2tm1Lau

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 120% more necrosis after experimental ischemia and reperfusion than found in controls
• 72% more polymorphonuclear neutrophiles per unit area in mid-ventricular slices relative to controls

homeostasis/metabolism
• 120% more necrosis after experimental ischemia and reperfusion than found in controls
• 72% more polymorphonuclear neutrophiles per unit area in mid-ventricular slices relative to controls


Mouse Genome Informatics
cx15
    Nos2tm1Lau/Nos2tm1Lau
Tg(APPSWE)2576Kha/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• plaque levels elevated in the brain relative to control mice carrying the transgene only (J:112919)
• deposits are observed by 52 weeks of age (J:143551)
• double mutant exhibits increased (3172 pg/ml v. 662 pg/ml) total deposits relative to control transgenic Tg(APPSWE)2576Kha (J:143551)
• ratio of Abeta40:Abeta42 in double mutant is increased (3.8 : 1.5) relative to control transgenic Tg(APPSWE)2576Kha (J:143551)
• neuronal loss in hippocampus, subiculum and CA3 is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha
• neuronal loss in hippocampus, subiculum and CA3 is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha
• neuronal loss in subiculum is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha
• widespread cortical neuron damage

behavior/neurological
• higher level of errors in day 2 of radial arm water maze in double mutant relative to single mutants Tg(APPSWE)2576Kha or homozygous Nostm1Lau

homeostasis/metabolism
• plaque levels elevated in the brain relative to control mice carrying the transgene only (J:112919)
• deposits are observed by 52 weeks of age (J:143551)
• double mutant exhibits increased (3172 pg/ml v. 662 pg/ml) total deposits relative to control transgenic Tg(APPSWE)2576Kha (J:143551)
• ratio of Abeta40:Abeta42 in double mutant is increased (3.8 : 1.5) relative to control transgenic Tg(APPSWE)2576Kha (J:143551)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:112919


Mouse Genome Informatics
cx16
    Nos2tm1Lau/Nos2tm1Lau
Tg(RHO-VEGFA)V-6Camp/0

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
• compared to mice carrying Tg(RHO-VEGFA)V-6Camp and heterozygous for Nos2tm1Lau neovascularization of the retina is significantly reduced


Mouse Genome Informatics
cx17
    Nos2tm1Lau/Nos2tm1Lau
Tg(Thy1-APPSwDutIowa)BWevn/?

involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• deposits are observed by 52 weeks of age
• 65% loss of NPY interneurons in the hippocampus
• neuronal loss is observed in hippocampus, subiculum and CA3

homeostasis/metabolism
• deposits are observed by 52 weeks of age