Phenotypes Associated with This Genotype

Genotype
MGI:5771865

• Allelic Composition: Apob^tm2Sgy/Apob^tm2Sgy; Ldlr^tm1Her/Ldlr^tm1Her; Tg(Ins-Igf2)1Fbos/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

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

homeostasis/metabolism

abnormal fasting circulating glucose level ( J:227165 )

♂ • fasting glycemia is increased on a standard chow diet

♂ • mice develop diabetes mellitus based on fasting hyperglycemia and lack of compensatory increase in insulin secretion when fed a high-fat/sucrose/cholesterol (HFSC) diet for 6 months

increased circulating insulin level ( J:227165 )

♂ • increase in fasting insulin levels on standard chow diet

increased circulating cholesterol level ( J:227165 )

♂ • mice exhibit cholesterolemia on both a standard chow diet and a high-fat/sucrose/cholesterol (HFSC) diet

cardiovascular system

abnormal aorta bulb morphology ( J:227165 )

♂ • mice fed the HFSC diet show higher expression of osteogenic genes in the aortic root

♂ • mice fed the HFSC diet show aortic root fibrosis

cardiac hypertrophy ( J:227165 )

♂ • HFSC-fed mice exhibit increased expression of hypertrophic cardiac markers

abnormal heart left ventricle morphology ( J:227165 )

♂ • increase in left ventricular mass on both a chow and HFSC diet

heart left ventricle hypertrophy ( J:227165 )

♂ • left ventricular hypertrophy in HFSC-fed mice

abnormal aortic valve morphology ( J:227165 )

♂ • mice fed the HFSC diet show aortic valve fibrosis

aortic valve stenosis ( J:227165 )

♂ • 80% of mice fed the HFSC diet for 6 months develop aortic stenosis, with mice showing increased peak aortic jet velocity, peak transvalvular pressure gradient, and mean transvalvular pressure gradient; magnitude of aortic stenosis is greater than in double Apob and Ldlr homozygotes

calcified aortic valve ( J:227165 )

♂ • HFSC-fed mice exhibit aortic valve calcification

small aortic valve ( J:227165 )

• aortic valve area is decreased in HFSC-fed mice

abnormal heart ventricles weight ( J:227165 )

♂ • total ventricular weight corrected for body weight is elevated in mice fed the HFSC diet

♂ • when corrected for tibia length, the total ventricular weight is increased in mice either on the chow or HFSC diet

cardiac fibrosis ( J:227165 )

♂ • mice fed the HFSC diet show aortic root fibrosis and aortic valve fibrosis

abnormal cardiovascular system physiology ( J:227165 )

♂ • echocardiography shows impaired left ventricular function in mice fed a chow diet with worsening cardiac dysfunction on the HFSC diet

♂ • the mitral E/E ratio (mitral inflow measured by pulsed-wave over tissue Doppler) is increased in mice on the HFSC diet

♂ • isovolumic relaxation time, corrected for heart rate, is decreased in mice on the HFSC diet

increased cardiac output ( J:227165 )

♂ • cardiac output is increased in mice fed the HFSC diet

increased cardiac stroke volume ( J:227165 )

♂ • stroke volume is increased in mice fed the HFSC diet

decreased cardiac muscle contractility ( J:227165 )

♂ • reduction in systolic fractional shortening in mice fed the HFSC diet

aortitis ( J:227165 )

♂ • some areas of the aortic surface leaflet from HFSC-fed mice are denuded of endothelial cells and show presence of inflammatory cell aggregates, platelets, and fibrin covering the extracellular matrix

immune system

aortitis ( J:227165 )

♂ • some areas of the aortic surface leaflet from HFSC-fed mice are denuded of endothelial cells and show presence of inflammatory cell aggregates, platelets, and fibrin covering the extracellular matrix

muscle

heart left ventricle hypertrophy ( J:227165 )

♂ • left ventricular hypertrophy in HFSC-fed mice

decreased cardiac muscle contractility ( J:227165 )

♂ • reduction in systolic fractional shortening in mice fed the HFSC diet

growth/size/body

cardiac hypertrophy ( J:227165 )

♂ • HFSC-fed mice exhibit increased expression of hypertrophic cardiac markers

heart left ventricle hypertrophy ( J:227165 )

♂ • left ventricular hypertrophy in HFSC-fed mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic valve disease		DOID:62		J:227165
type 1 diabetes mellitus 2		DOID:0110741	OMIM:125852	J:227165