Phenotypes associated with this allele

• Allele Symbol: Ncf1^tm1Shl
• Allele Name: targeted mutation 1, Steven M Holland
• Allele ID: MGI:1934143
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ncf1^tm1Shl/Ncf1^tm1Shl	B6.129S2-Ncf1^tm1Shl	MGI:4438111
hm2	Ncf1^tm1Shl/Ncf1^tm1Shl	involves: 129S2/SvPas	MGI:5569389
hm3	Ncf1^tm1Shl/Ncf1^tm1Shl	involves: 129S2/SvPas * C57BL/6J	MGI:2175140
cx4	Apoe^tm1Unc/Apoe^tm1Unc Ncf1^tm1Shl/Ncf1^tm1Shl	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:4438110

Genotype
MGI:4438111

hm1

• Allelic Composition: Ncf1^tm1Shl/Ncf1^tm1Shl
• Genetic Background: B6.129S2-Ncf1^tm1Shl

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

growth/size/body

cardiac hypertrophy ( J:133916 )

• greatly reduced after myocardial infarction relative to controls

abnormal postnatal growth ( J:142617 )

• weight gain on a high fat diet is more moderate than in controls

cardiovascular system

abnormal angiogenesis ( J:142617 )

• angiogenic response after carotid ligation is more moderate than in controls

abnormal heart morphology ( J:133916 )

cardiac hypertrophy ( J:133916 )

• greatly reduced after myocardial infarction relative to controls

dilated heart left ventricle ( J:133916 )

• left ventricular cavity dilation is substantially reduced after myocardial infarction

abnormal cardiovascular system physiology ( J:111142 )

abnormal cardiac muscle contractility ( J:133916 )

• left ventricular ejection fraction is better preserved than in infarcted controls

abnormal response to cardiac infarction ( J:133916 )

• improved survival rate (72% vs 48% for controls)

• reduced apoptosis at the left ventricular border zone

• myocardial hypertrophy largely prevented

increased systemic arterial blood pressure ( J:111142 )

• elevated blood pressure between 6-12 weeks of age

• blood pressure slowly decreases with age

abnormal vascular smooth muscle physiology ( J:111142 )

• endothelium dependent relaxation by acetyl choline in aortic rings is attenuated at 12 weeks

abnormal vascular wound healing ( J:142617 )

• more moderate neointimal formation after carotid ligation relative to controls

immune system

abnormal inflammatory response ( J:142617 )

• inflammatory response after carotid ligation is more moderate than in controls

granulomatous inflammation ( J:111142 )

• lung granuloma formation after 12 weeks if not treated with antibiotics

• lung granuloma formation after 20 weeks when treated with antibiotics

homeostasis/metabolism

abnormal response to cardiac infarction ( J:133916 )

• improved survival rate (72% vs 48% for controls)

• reduced apoptosis at the left ventricular border zone

• myocardial hypertrophy largely prevented

abnormal vascular wound healing ( J:142617 )

• more moderate neointimal formation after carotid ligation relative to controls

increased circulating renin level ( J:111142 )

• at 12 weeks

increased angiotensin I-converting enzyme activity ( J:111142 )

• elevated ACE activity in tissues at 12 weeks of age

nervous system

enhanced long-term potentiation ( J:111410 )

• long lasting phase of LTP is slightly enhanced

reduced long-term potentiation ( J:111410 )

• completely abrogated in hippocampal slices

behavior/neurological

impaired cued conditioning behavior ( J:111410 )

• impaired contextual fear response

• cued memory is normal

abnormal spatial learning ( J:111410 )

• small but significant deficits in early training trials in water maze tests

• spatial learning impairments

abnormal locomotor activation ( J:111410 )

• slightly increased time spent in the center in an open field test

muscle

abnormal cardiac muscle contractility ( J:133916 )

• left ventricular ejection fraction is better preserved than in infarcted controls

abnormal vascular smooth muscle physiology ( J:111142 )

• endothelium dependent relaxation by acetyl choline in aortic rings is attenuated at 12 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic granulomatous disease		DOID:3265	OMIM:PS306400	J:111142

Genotype
MGI:5569389

hm2

• Allelic Composition: Ncf1^tm1Shl/Ncf1^tm1Shl
• Genetic Background: involves: 129S2/SvPas

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:206181 )

• goblet cells exhibit increased mucin accumulation compared with control cells

cellular

abnormal intestinal goblet cell morphology ( J:206181 )

• goblet cells exhibit increased mucin accumulation compared with control cells

Genotype
MGI:2175140

hm3

• Allelic Composition: Ncf1^tm1Shl/Ncf1^tm1Shl
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

Ncf1^tm1Shl/Ncf1^tm1Shl mice develop lethal infections and granulomatous inflammation

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:28267 )

• following infection with the types of organisms characteristic of human Chronic Granulomatous Disease (CGD) such as Staphylococcus and Lactobacillus, mice exhibit lethal infections not observed in wild-type mice

immune system

increased acute inflammation ( J:28267 )

• following intraperitoneal injection with thioglycollate, mice exhibit an abnormally exuberant inflammation recruiting twice as many leukocytes as in wild-type mice

abnormal response to infection ( J:28267 )

• impaired phagocytic response to Staphylococcal infection such that they produce no superoxide and kill Staphylococcus ineffectively

increased susceptibility to infection ( J:28267 )

• unlike wild-type mice, mice develop severe infections in response to types of organisms characteristic of human Chronic Granulomatous Disease (CGD) such as Staphylococcus and Lactobacillus

• infections are characterized by adenopathy, splenomegaly, and granulomatous pneumonia with neutrophils, plasma cells, lymphocytes, macrophages and multinucleated giant cells

cardiovascular system

decreased vasoconstriction ( J:120187 )

• hypoxic pulmonary vasoconstriction is significantly lower than for B6.129S-Cybb^tm1Din or B6 controls

• esponse is primarily in the acute phase of the vasoconstrictor response while the sustained phase is similar to controls

muscle

decreased vasoconstriction ( J:120187 )

• hypoxic pulmonary vasoconstriction is significantly lower than for B6.129S-Cybb^tm1Din or B6 controls

• esponse is primarily in the acute phase of the vasoconstrictor response while the sustained phase is similar to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic granulomatous disease		DOID:3265	OMIM:PS306400	J:28267

Genotype
MGI:4438110

cx4

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Ncf1^tm1Shl/Ncf1^tm1Shl
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

cardiovascular system

abnormal susceptibility to atherosclerosis ( J:154332 )

• development of atherosclerosis is considerably reduced 2 weeks after ligation of the left common carotid as compared to Apoe^tm1Unc

• atherosclerosis continues to be reduced 3 weeks after ligation of the left common carotid as compared to Apoe^tm1Unc but no longer significantly

abnormal descending thoracic aorta morphology ( J:123854 )

• aneurysms reduced to 17% of animals rather than 40% as seen in Apoe^tm1Unc mice

aortic aneurysm ( J:123854 )

• aneurisms reduced to 17% of animals rather than 90% as seen in Apoe^tm1Unc mice

• diameter and weight of aneurisms considerably reduced relative to Apoe^tm1Unc mice but still enlarged relative to controls

decreased systemic arterial systolic blood pressure ( J:123854 )

• angiotensin-II induced affect on blood pressure is blunted

immune system

decreased acute inflammation ( J:123854 )

• leukocyte infiltration into the adventitia of the aorta is attenuated