Phenotypes associated with this allele

• Allele Symbol: Yme1l1^tm1Tlan
• Allele Name: targeted mutation 1, Thomas Langer
• Allele ID: MGI:5629742
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * C57BL/6NCrl * FVB	MGI:5805260
cn2	Oma1^tm1Tlan/Oma1^tm1Tlan Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * C57BL/6NCrl * FVB	MGI:5805262
cn3	Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6NCrl * FVB/N	MGI:5805256
cn4	Oma1^tm1Tlan/Oma1^tm1Tlan Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6NCrl * FVB/N	MGI:5805258

Genotype
MGI:5805260

cn1

• Allelic Composition: Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB

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

homeostasis/metabolism

decreased circulating insulin level ( J:229455 )

• lowered fasting insulin levels in the serum

• however, mice exhibit normal fasting blood glucose, weight gains and body composition

impaired glucose tolerance ( J:229455 )

• glucose intolerance

cardiovascular system

cardiovascular system phenotype ( J:229455 )

N • mice show normal heart function and normal cardiac uptake of glucose smaller mitochondria in hearts

mortality/aging

mortality/aging ( J:229455 )

N • mice show a normal life span, with a median life span of 125 weeks

Genotype
MGI:5805262

cn2

• Allelic Composition: Oma1^tm1Tlan/Oma1^tm1Tlan; Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:229455 )

N • mice exhibit normal glucose tolerance

Genotype
MGI:5805256

cn3

• Allelic Composition: Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB/N

mortality/aging

premature death ( J:229455 )

• median lifespan of 46 weeks

cardiovascular system

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

abnormal heart morphology ( J:229455 )

• hearts show increased endogenous glucose levels and decreased lactate levels

• however, levels of citric acid cycle intermediates are not altered

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

dilated heart left ventricle ( J:229455 )

• dilated left ventricular chamber

• however, left ventricular mass is preserved

cardiac fibrosis ( J:229455 )

• myocardial fibrosis

abnormal cardiovascular system physiology ( J:229455 )

• progressive heart dysfunction which becomes apparent at 20 weeks

• mice fed a high-fat diet beginning at 9 weeks of age show normal cardiac glucose uptake, normal levels of endogenous cardiac glucose and acylcarnitine, restoration of cardiac function, prevention of cardiac fibrosis, normal exercise tolerance and left ventricular ejection fraction, suppressed heart failure and restored life span

dilated cardiomyopathy ( J:229455 )

• dilated cardiomyopathy progresses to heart failure in middle age

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased heart left ventricle muscle contractility ( J:229455 )

• reduction in percentage of left ventricular ejection fraction

congestive heart failure ( J:229455 )

growth/size/body

weight loss ( J:229455 )

• weight loss before death

homeostasis/metabolism

increased circulating troponin T level ( J:229455 )

• increase in serum cardiac troponin T levels

cellular

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased mitochondrial size ( J:229455 )

• smaller mitochondria with normal cristae architecture in hearts

abnormal mitochondrial physiology ( J:229455 )

• specific activities of mitochondrial complexes II, III, and IV are increased in cardiomyocytes

• only moderately impaired ATP synthesis by complex V in hearts

muscle

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

abnormal muscle physiology ( J:229455 )

• in vitro cardiomyocyte glycolysis rates are increased

• global reduction of total cardiac acylcarnitines, indicating reduced beta oxidation in cardiomyocytes

dilated cardiomyopathy ( J:229455 )

• dilated cardiomyopathy progresses to heart failure in middle age

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased heart left ventricle muscle contractility ( J:229455 )

• reduction in percentage of left ventricular ejection fraction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:229455

Genotype
MGI:5805258

cn4

• Allelic Composition: Oma1^tm1Tlan/Oma1^tm1Tlan; Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:229455 )

N • mice exhibit normal cardiac function and mitochondrial morphology in hearts, and do not exhibit myocardial fibrosis