Phenotypes Associated with This Genotype

Genotype
MGI:5428952

• Allelic Composition: Ndufs6^{Gt(AR0138)Wtsi}/Ndufs6^{Gt(AR0138)Wtsi}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

Cardiac abnormalities in Ndufs6^{Gt(AR0138)Wtsi}/Ndufs6^{Gt(AR0138)Wtsi} mice

mortality/aging

premature death ( J:183619 )

• prone to rapid onset of weight loss and sudden death starting at 4 and 8 months of age in males and females, respectively

• long term survival of males is about half that of females

growth/size/body

enlarged heart ( J:183619 )

• evident by 30 days of age and more pronounced in males

• enlargement is more severe in mice with weight loss

increased heart weight ( J:183619 )

• near doubling of heart weight and heart to body weight ratio

weight loss ( J:183619 )

• prone to rapid onset of weight loss starting at 4 and 8 months of age in males and females, respectively

cardiovascular system

enlarged heart ( J:183619 )

• evident by 30 days of age and more pronounced in males

• enlargement is more severe in mice with weight loss

increased heart weight ( J:183619 )

• near doubling of heart weight and heart to body weight ratio

increased heart ventricle size ( J:183619 )

increased heart left ventricle size ( J:183619 )

• increase in chamber dimensions and wall thickness

• left ventricular end-systolic and end-diastolic diameters and posterior wall thickness are increased

increased heart left ventricle weight ( J:183619 )

• increase in free wall and septal weights

increased heart right ventricle size ( J:183619 )

• increase in chamber dimensions and wall thickness

increased heart right ventricle weight ( J:183619 )

• increase in free wall and septal weights

cardiac fibrosis ( J:183619 )

• scattered areas of fibrosis

abnormal cardiovascular system physiology ( J:183619 )

• aortic output, coronary flow and left ventricular stroke volume are reduced

• hearts are situated at the lower end of a highly linear stroke volume?external work relationship

• cardiac failure in mice with weight loss

decreased ventricle muscle contractility ( J:183619 )

• decrease in fractional shortening

abnormal cardiac muscle relaxation ( J:183619 )

• left ventricular relaxation is reduced

decreased left ventricle systolic pressure ( J:183619 )

• at baseline preload peak systolic pressure is reduced

increased left ventricle diastolic pressure ( J:183619 )

• at baseline preload end diastolic pressure is increased

cellular

abnormal mitochondrial morphology ( J:183619 )

• in the ventricular myocardium mitochondria appear abnormal with the central area frequently denser than the periphery due to narrowing of both the matrix and intercristal spaces

decreased mitochondrial size ( J:183619 )

• decrease in mitochondrial area in the ventricular myocardium

abnormal respiratory electron transport chain ( J:183619 )

• mitochondrial complex I activity is about 10% that in wild-type mitochondria

reproductive system

decreased litter size ( J:183619 )

• females produce smaller litters and have reduced pup survival rates

homeostasis/metabolism

increased fatty acids level ( J:183619 )

• general increase in hydroxyacylcarnitines with chain length C6 to C18 in the heart

muscle

decreased ventricle muscle contractility ( J:183619 )

• decrease in fractional shortening

abnormal cardiac muscle relaxation ( J:183619 )

• left ventricular relaxation is reduced

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial complex I deficiency		DOID:0060536	OMIM:252010	J:183619