Mouse Genome Informatics
hm1
    Acadvltm1Vje/Acadvltm1Vje
involves: 129/Sv * Black Swiss * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• exhibit a decrease in survival after short exposure to cold and fasting unlike wild-type

adipose tissue
• brown adipose tissue shows elevated levels of the uncoupling protein isoforms and peroxisome proliferators-activated receptor-alpha
• brown adipose tissue shows increased oxygen consumption, attributed to uncoupled respiration in the absence of stress

cardiovascular system
• exhibit microvesicular fat infiltration of cardiomyocytes (cardiac lipidosis) after combined stresses of fasting and cold that are not observed in wild-type
• 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
• 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
• develop decreased body temperature during the combined stresses of fasting and cold
• 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
• develop low blood sugar levels during the combined stresses of fasting and cold
• the decrease in liver glycogen levels during the combined stresses of fasting and cold is more pronounced in homozygotes than controls

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

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


Mouse Genome Informatics
hm2
    Acadvltm1Vje/Acadvltm1Vje
involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 4 of 12 homozygotes become moribund or die during an 8 hour fasting period at 4 degrees Celsius compared to none of the controls
• exhibit unexpected sudden death later in life

cardiovascular system
• 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
• exhibit increased numbers of degenerative fibers
• increased susceptibility to the induction of polymorphic ventricular arrhythmias in the absence of systolic dysfunction and absence of exogenously imposed stress
• characterized by abnormal myocardial histology and increased arrhythmia susceptibility

muscle
• 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
• exhibit increased numbers of degenerative fibers
• characterized by abnormal myocardial histology and increased arrhythmia susceptibility
• soleus muscle shows marked mitochondrial proliferation, particularly in the subsarcolemmal area, and irregularly sized and chaotically palisaded mitochondria

adipose tissue
• exhibit increased visceral and cardiac fat storage later in life

homeostasis/metabolism
• mean body temperature drops significantly more after 8 hours at 4 degrees Celsius than in controls and shivering is not observed
• 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
• 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
• run at a significantly lower maximum speed compared to controls when exercise to exhaustion on a treadmill

growth/size/body
• body weight increases later in life

tumorigenesis
• develop abdominal tumors later in life


Mouse Genome Informatics
ht3
    Acadvltm1Vje/Acadvl+
involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 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