Phenotypes associated with this allele

• Allele Symbol: Acadvl^tm1Vje
• Allele Name: targeted mutation 1, Vernat J Exil
• Allele ID: MGI:3606688
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Acadvl^tm1Vje/Acadvl^tm1Vje	involves: 129/Sv * Black Swiss * C57BL/6	MGI:3655859
hm2	Acadvl^tm1Vje/Acadvl^tm1Vje	involves: 129/Sv * C57BL/6	MGI:3607794
ht3	Acadvl^tm1Vje/Acadvl^+	involves: 129/Sv * C57BL/6	MGI:3607795

Genotype
MGI:3655859

hm1

• Allelic Composition: Acadvl^tm1Vje/Acadvl^tm1Vje
• Genetic Background: involves: 129/Sv * Black Swiss * C57BL/6

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:106714 )

• exhibit a decrease in survival after short exposure to cold and fasting unlike wild-type

adipose tissue

abnormal brown adipose tissue morphology ( J:106714 )

• brown adipose tissue shows elevated levels of the uncoupling protein isoforms and peroxisome proliferators-activated receptor-alpha

abnormal brown adipose tissue physiology ( J:106714 )

• brown adipose tissue shows increased oxygen consumption, attributed to uncoupled respiration in the absence of stress

cardiovascular system

abnormal myocardial fiber morphology ( J:106714 )

• exhibit microvesicular fat infiltration of cardiomyocytes (cardiac lipidosis) after combined stresses of fasting and cold that are not observed in wild-type

decreased heart rate ( J:106714 )

• develop severe bradycardia with the combination of fasting and cold stress

• glucose administration in conjunction with rewarming or rewarming alone (but not glucose alone) reverse the bradycardia and rescue the mice

cellular

abnormal cellular respiration ( J:106714 )

• exhibit abnormal mitochondrial bioenergetics of brown adipose tissue after the combination of fasting and cold stresses, as evident by altered mitochondrial oxygen consumption and terminally uncoupled mitochondria

homeostasis/metabolism

impaired adaptive thermogenesis ( J:106714 )

• develop decreased body temperature during the combined stresses of fasting and cold

abnormal amino acid level ( J:106714 )

• upon exposure to stresses of fasting alone or cold alone, mutants are able to maintain normal blood glucose levels, however levels of C16 and C18 acylcarnitines are elevated

hypoglycemia ( J:106714 )

• develop low blood sugar levels during the combined stresses of fasting and cold

decreased glycogen level ( J:106714 )

• the decrease in liver glycogen levels during the combined stresses of fasting and cold is more pronounced in homozygotes than controls

liver/biliary system

macrovesicular hepatic steatosis ( J:106714 )

• exhibit severe macrovesicular hepatic steatosis after the combined stresses of fasting and cold whereas only see minimal fat infiltration in wild-type livers

muscle

abnormal myocardial fiber morphology ( J:106714 )

• exhibit microvesicular fat infiltration of cardiomyocytes (cardiac lipidosis) after combined stresses of fasting and cold that are not observed in wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
very long chain acyl-CoA dehydrogenase deficiency		DOID:0080155	OMIM:201475	J:106714

Genotype
MGI:3607794

hm2

• Allelic Composition: Acadvl^tm1Vje/Acadvl^tm1Vje
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:102010 )

• 4 of 12 homozygotes become moribund or die during an 8 hour fasting period at 4 degrees Celsius compared to none of the controls

premature death ( J:102010 )

• exhibit unexpected sudden death later in life

cardiovascular system

abnormal myocardial fiber morphology ( J:98627 )

• exhibit increased numbers of degenerative fibers, collagen deposition, vacuolated myocytes, and increased fat deposition/lipid accumulation in myocytes

• exhibit an increase in mitochondria numbers and mitochondrial cross sectional area and observe scattered bizarre and giant mitochondria in cardiomyoctes

myocardial fiber degeneration ( J:98627 )

• exhibit increased numbers of degenerative fibers

irregular heartbeat ( J:98627 )

• increased susceptibility to the induction of polymorphic ventricular arrhythmias in the absence of systolic dysfunction and absence of exogenously imposed stress

cardiomyopathy ( J:98627 )

• characterized by abnormal myocardial histology and increased arrhythmia susceptibility

muscle

abnormal myocardial fiber morphology ( J:98627 )

• exhibit increased numbers of degenerative fibers, collagen deposition, vacuolated myocytes, and increased fat deposition/lipid accumulation in myocytes

• exhibit an increase in mitochondria numbers and mitochondrial cross sectional area and observe scattered bizarre and giant mitochondria in cardiomyoctes

myocardial fiber degeneration ( J:98627 )

• exhibit increased numbers of degenerative fibers

cardiomyopathy ( J:98627 )

• characterized by abnormal myocardial histology and increased arrhythmia susceptibility

abnormal skeletal muscle fiber morphology ( J:98627 )

• soleus muscle shows marked mitochondrial proliferation, particularly in the subsarcolemmal area, and irregularly sized and chaotically palisaded mitochondria

adipose tissue

abnormal adipose tissue morphology ( J:102010 )

• exhibit increased visceral and cardiac fat storage later in life

homeostasis/metabolism

impaired adaptive thermogenesis ( J:102010 )

• mean body temperature drops significantly more after 8 hours at 4 degrees Celsius than in controls and shivering is not observed

abnormal amino acid level ( J:102010 )

• under well-fed, nonstressed conditions, show an accumulation of long-chain acylcarnitines, with a 2-3-fold increase of the C16 and C18 acylcarnitines and a 2-fold increase in the C20-C24 acylcarnitines, however acetylcarnitine (C2) was reduced and mean free carnitine is reduced to 72% in homozygotes compared to wild-type

• after intense exercise or cold challenge with fasting, sum of C14-C18 long chain acylcarnitines increased compared to wild-type

impaired glucose tolerance ( J:102010 )

• after 8 hours of fasting at 4 degrees Celsius, mean glucose levels decreased more than in controls and did not stabilize at the same levels as in controls

behavior/neurological

fatigue ( J:102010 )

• run at a significantly lower maximum speed compared to controls when exercise to exhaustion on a treadmill

growth/size/body

increased body weight ( J:102010 )

• body weight increases later in life

neoplasm

increased tumor incidence ( J:102010 )

• develop abdominal tumors later in life

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
very long chain acyl-CoA dehydrogenase deficiency		DOID:0080155	OMIM:201475	J:98627 , J:102010

Genotype
MGI:3607795

ht3

• Allelic Composition: Acadvl^tm1Vje/Acadvl⁺
• Genetic Background: involves: 129/Sv * C57BL/6

homeostasis/metabolism

abnormal amino acid level ( J:102010 )

• mean free carnitine is reduced to 88% in heterozygotes compared with wild-type under normal conditions

• after intense exercise or cold challenge with fasting, sum of C14-C18 acylcarnitines increased compared to wild-type but not as much as in homozygotes