Phenotypes associated with this allele

• Allele Symbol: Col1a1^{tm2(CAG-IDH2*R172K)Kkw}
• Allele Name: targeted mutation 2, Kwok-Kin Wong
• Allele ID: MGI:5582206
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Col1a1^tm2(CAG-IDH2*R172K)Kkw/Col1a1^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S4/SvJae * BALB/c * C57BL/6	MGI:5582235

Genotype
MGI:5582235

cn1

• Allelic Composition: Col1a1^{tm2(CAG-IDH2*R172K)Kkw}/Col1a1⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * BALB/c * C57BL/6

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

mortality/aging

premature death ( J:209629 )

• mean survival after tamoxifen administration is 4 weeks

respiratory system

respiratory distress ( J:209629 )

• mice show shortness of breath within 3-4 weeks of tamoxifen administration

behavior/neurological

lethargy ( J:209629 )

• mice show signs of lethargy within 3-4 weeks of tamoxifen administration

cardiovascular system

blood vessel congestion ( J:209629 )

• microscopic signs of circulatory congestion associated with cardiac failure are seen after tamoxifen administration

increased cardiac muscle glycogen level ( J:209629 )

• cardiac muscle shows glycogen accumulation in tamoxifen treated mice

abnormal myocardial fiber morphology ( J:209629 )

• myocyte dropout associated with myocyte hypertrophy and nuclear enlargement 4 weeks after tamoxifen administration

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administration, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

enlarged heart ( J:209629 )

• heart enlargement after tamoxifen administration

cardiac fibrosis ( J:209629 )

• seen after tamoxifen treatment

dilated cardiomyopathy ( J:209629 )

• 4 weeks after tamoxifen administration, mice exhibit end-stage cardiomyopathy characterized by severely decreased wall motion and increased dilatation without a change in heart rate

• 4 weeks after tamoxifen administration, mice show scarring of the hearts associated with accumulating collagen deposits

decreased cardiac muscle contractility ( J:209629 )

• fractional shortening is decreased in tamoxifen treated mice

cellular

abnormal mitochondrial morphology ( J:209629 )

• evidence of mitophagy is seen in tamoxifen treated mice, as indicated by the presence of double-membrane autophagosomes

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal mitochondrial crista morphology ( J:209629 )

• disrupted cristae in cardiomyocytes of tamoxifen treated mice

abnormal skeletal muscle fiber mitochondrial morphology ( J:209629 )

• skeletal muscle shows abnormalities in mitochondria after tamoxifen administration

decreased mitochondrial number ( J:209629 )

• in cardiomyocytes of tamoxifen treated mice

increased cardiomyocyte apoptosis ( J:209629 )

• cardiac defects in tamoxifen treated mice are associated with high levels of apoptosis in cardiomyocytes

abnormal mitochondrial physiology ( J:209629 )

• decrease in the steady-state mitochondrial TCA cycle intermediates in mice treated with tamoxifen

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:209629 )

• cardiac muscle shows glycogen accumulation in tamoxifen treated mice

increased skeletal muscle glycogen level ( J:209629 )

• skeletal muscle shows glycogen accumulation in tamoxifen treated mice

muscle

increased cardiac muscle glycogen level ( J:209629 )

• cardiac muscle shows glycogen accumulation in tamoxifen treated mice

abnormal myocardial fiber morphology ( J:209629 )

• myocyte dropout associated with myocyte hypertrophy and nuclear enlargement 4 weeks after tamoxifen administration

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administration, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

dilated cardiomyopathy ( J:209629 )

• 4 weeks after tamoxifen administration, mice exhibit end-stage cardiomyopathy characterized by severely decreased wall motion and increased dilatation without a change in heart rate

• 4 weeks after tamoxifen administration, mice show scarring of the hearts associated with accumulating collagen deposits

decreased cardiac muscle contractility ( J:209629 )

• fractional shortening is decreased in tamoxifen treated mice

increased cardiomyocyte apoptosis ( J:209629 )

• cardiac defects in tamoxifen treated mice are associated with high levels of apoptosis in cardiomyocytes

abnormal sarcomere morphology ( J:209629 )

• cardiomyocytes show sarcomere degeneration and severe disorganization at 4 weeks after tamoxifen administration

• skeletal muscle shows abnormalities in sarcomere organization after tamoxifen administration

abnormal Z line morphology ( J:209629 )

• cardiac Z disks are perturbed in mice treated with tamoxifen

abnormal skeletal muscle morphology ( J:209629 )

• skeletal muscle shows abnormalities in sarcomere organization, mitochondria, and glycogen accumulation in tamoxifen treated mice

abnormal skeletal muscle fiber mitochondrial morphology ( J:209629 )

• skeletal muscle shows abnormalities in mitochondria after tamoxifen administration

increased skeletal muscle glycogen level ( J:209629 )

• skeletal muscle shows glycogen accumulation in tamoxifen treated mice

skeletal muscle fiber degeneration ( J:209629 )

• myofiber regeneration and degeneration are seen following tamoxifen administration

skeletal muscle fiber necrosis ( J:209629 )

• seen following tamoxifen administration

skeletal muscle endomysial fibrosis ( J:209629 )

• seen following tamoxifen administration

nervous system

brain vacuoles ( J:209629 )

• mice treated with tamoxifen exhibit vacuoles in multiple brain regions, including cortex, white matter, hippocampus, and brain stem

• vacuoles are filled with membranous debris at both myelinated axons and nonmyelinated naked axons but not in the neuron bodies

neurodegeneration ( J:209629 )

• diffuse vacuolar leukoencephalopathy in the white and gray matter throughout the CNS of tamoxifen treated mice

• vesicles are double-membraned, suggesting elevation in autophagy and mitochondrial abnormalities in axons of the brain

• however, no evidence of apoptosis or glycogen accumulation is seen in the brain

growth/size/body

enlarged heart ( J:209629 )

• heart enlargement after tamoxifen administration