Phenotypes Associated with This Genotype

Genotype
MGI:5906283

• Allelic Composition: Tg(APCS-Ifng)5Imeg/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

mortality/aging

premature death ( J:16979 )

• mice die around 6 months of age under conventional conditions

• about 80% of mice die by 1 year of age under specific-pathogen-free conditions

cardiovascular system

liver vascular congestion ( J:135124 )

• mice exhibit congestive liver alternations such as centrolobular, sinusoidal dilation, trabecular atrophy, and centrolobular fatty degeneration

cardiac muscle atrophy ( J:135124 )

• by 6 months of age, atrophy of the heart musculature is seen

cardiac muscle degeneration ( J:135124 )

• at 6 months of age, hearts show enhanced myodegenerative alterations

abnormal heart morphology ( J:135124 )

• signs of disseminated cardiomyolysis is seen in 2 month old hearts

abnormal myocardial fiber morphology ( J:135124 )

• drop-out and variation in size and shape of cardiac muscle fibers at 6 months of age and is more pronounced in moribund mice at around 10 months of age

dilated heart left ventricle ( J:135124 )

cardiac interstitial fibrosis ( J:135124 )

• reactive interstitial fibrosis with deposition of extracellular matrix is seen in 6 month old hearts

dilated cardiomyopathy ( J:135124 )

decreased cardiac muscle contractility ( J:135124 )

• fractional shortening is decreased

abnormal heart echocardiography feature ( J:135124 )

• echocardiography shows an increase of relative left ventricular mass and of left ventricular end diastolic and end systolic diameter in 6 month old mice

• fractional shortening, interventricular septum and posterior wall thickness are decreased

myocarditis ( J:135124 )

• low-level interstitial mononuclear infiltrate is seen in hearts of 2 month old mice

• mononuclear infiltrations are comprised of abundant CD4+ T cells, CD8+ T cells, Mac2+ macrophages, and CD11x+ dendritic cells

• mice show infiltrations with Mac2+ macrophages and CD3+ T cells

• however, almost no B220+ B cells are detected

• no inflammatory changes or signs of tissue damage are seen in striated skeletal musculature and various sites of smooth muscle such as large blood vessels and the intestinal tract at 6 months of age

endocrine/exocrine glands

pancreas inflammation ( J:135124 )

• slight mononuclear infiltrates are detected in the exocrine pancreas of 6 month old mice

homeostasis/metabolism

abnormal circulating enzyme level ( J:16979 )

• plasma levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase are elevated, suggesting liver cell injury

• both glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels increase gradually with age

increased circulating alanine transaminase level ( J:135124 )

• alanine transaminase serum concentrations are elevated in 6 month old mice

abnormal cytokine level ( J:135124 )

♂ • hearts exhibit high-level expression of proinflammatory cytokines at 6 months of age

increased circulating interleukin-12 level ( J:135124 )

immune system

myocarditis ( J:135124 )

• low-level interstitial mononuclear infiltrate is seen in hearts of 2 month old mice

• mononuclear infiltrations are comprised of abundant CD4+ T cells, CD8+ T cells, Mac2+ macrophages, and CD11x+ dendritic cells

• mice show infiltrations with Mac2+ macrophages and CD3+ T cells

• however, almost no B220+ B cells are detected

• no inflammatory changes or signs of tissue damage are seen in striated skeletal musculature and various sites of smooth muscle such as large blood vessels and the intestinal tract at 6 months of age

pancreas inflammation ( J:135124 )

• slight mononuclear infiltrates are detected in the exocrine pancreas of 6 month old mice

abnormal cytokine level ( J:135124 )

♂ • hearts exhibit high-level expression of proinflammatory cytokines at 6 months of age

increased circulating interleukin-12 level ( J:135124 )

liver inflammation ( J:16979 )

• acute hepatitis is seen at 17 weeks of age

• necroinflammmation begins to appear randomly in liver lobules around 3 weeks of age and becomes prominent with age

• from 5 weeks of age, lymphoid cell infiltration appears at the portal area

chronic liver inflammation ( J:135124 )

• chronic active hepatitis

liver/biliary system

liver inflammation ( J:16979 )

• acute hepatitis is seen at 17 weeks of age

• necroinflammmation begins to appear randomly in liver lobules around 3 weeks of age and becomes prominent with age

• from 5 weeks of age, lymphoid cell infiltration appears at the portal area

chronic liver inflammation ( J:135124 )

• chronic active hepatitis

abnormal liver morphology ( J:16979 )

• at 37 weeks of age, ductal proliferation in the liver is seen

liver vascular congestion ( J:135124 )

• mice exhibit congestive liver alternations such as centrolobular, sinusoidal dilation, trabecular atrophy, and centrolobular fatty degeneration

liver fibrosis ( J:16979 )

• slight liver fibrosis appears from 26 weeks of age

muscle

abnormal myocardial fiber morphology ( J:135124 )

• drop-out and variation in size and shape of cardiac muscle fibers at 6 months of age and is more pronounced in moribund mice at around 10 months of age

cardiac muscle atrophy ( J:135124 )

• by 6 months of age, atrophy of the heart musculature is seen

cardiac muscle degeneration ( J:135124 )

• at 6 months of age, hearts show enhanced myodegenerative alterations

dilated cardiomyopathy ( J:135124 )

decreased cardiac muscle contractility ( J:135124 )

• fractional shortening is decreased

cellular

cardiac interstitial fibrosis ( J:135124 )

• reactive interstitial fibrosis with deposition of extracellular matrix is seen in 6 month old hearts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:135124
hepatitis		DOID:2237		J:16979