Analysis Tools
adipose tissue
|
• 7 month or older males accumulated more body fat than controls
|
|
• percent body fat in 18- and 24-week old females but not males was greater than in wildtype and saw no differences in lean mass
|
behavior/neurological
|
• homozygous mutants made significantly fewer entries into, spent significantly less time in, and traveled a significantly shorter distance in the central area of the field, although differences in distance traveled in the peripheral zone of the field was not significantly different from controls
|
|
• impaired strength as homozygotes were unable to remain on an inverted screen for the same length of time as wildtype but did not differ in the times that it took to turn around and climb to the top of screens
|
|
• homozygous mutants exhibited a significantly lower mean number of ambulations and rearings over a one hour period
|
|
• homozygous mutants exhibited a reduced capacity to sustain running exercise on a motorized treadmill at 3.5 and 6-8 months of age
|
cardiovascular system
|
• weight of the heart, but not brain. liver, kidney or brown adipose tissue (BAT), was significantly lower in 3 and 8 week old mutants
|
|
• hearts isolated from homozygous mutants generated lower cardiac work due to a reduced cardiac output than in wildtype
|
|
• left ventricular fractional shortening was decreased in 6-8 month old females during the first 4 minutes after exercise
|
|
• 6-8 month old females exhibited an inappropriate decline in the mean heart rate after exercise
• 10-12 week old mice exhibited a significantly blunted heart rate response to beta-adrenergic stimulation
|
cellular
|
• mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle
• soleus muscle had a defect in state 3 (ADP-stimulated) mitochondrial respiration, but not state 2 (basal) or state 4 respiration
• isolated hepatocytes exhibited a modest but significant reduction in both state 2 (basal) and 3 (ADP-stimulated) mitochondrial respiration rates
|
growth/size/body
|
• 15-20% reduction in total body mass 1 week after birth with this difference disappearing by 3 weeks of age
• modest but significant increase in body weight at 18 weeks of age
|
|
• modest but significant increase in body weight at 18 weeks of age with no differences in food intake or general activity
|
homeostasis/metabolism
|
• 28-37 day old mutants but not older mice, exhibited a markedly abnormal drop in core temperature (by 12C versus 3C in wildtype) when exposed to 4C for 5 hours
|
|
• the VO2max (maximum oxygen consumption, measured in milliliters of oxygen per kilogram of body weight per minute) was significantly lower in homozygous mutants than in wildtype when exercised on a rigorous treadmill protocol
|
|
• females on a high-fat diet were significantly more glucose tolerant compared to wildtype
|
|
• females on a high-fat diet were significantly more insulin sensitive compared to wildtype
|
liver/biliary system
|
• under basal conditions, the liver was normal, however following a 24 hour fast, homozygous mutants exhibited hepatic steatosis but showed no differences in plasma triglycerides or free fatty acids in fed or fasted states
|
|
• isolated hepatocytes exhibited a modest but significant reduction in both state 2 (basal) and 3 (ADP-stimulated) mitochondrial respiration rates
• hepatocytes treated with oleate accumulated more neutral lipid and had significantly lower rates of 3H-palmitate oxidation, indicating reduced capacity for fat oxidation
• triglyceride synthesis rate was increased nearly 50% in isolated homozygous mutant hepatocytes
|
muscle
|
• left ventricular fractional shortening was decreased in 6-8 month old females during the first 4 minutes after exercise
|
|
• weight of the gastrocnemius was significantly lower in 3 and 8 week old mutants
|
|
• weight of the soleus was significantly lower in 3 and 8 week old mutants
|
|
• fewer and smaller mitochondria and a reduction in the expression of nuclear genes involved in mitochondrial electron transport and oxidative phosphorylation were observed in the slow twitch fiber-enriched soleus muscle of 1 month old mutants, however no differences in mitochondrial ultrastructure were seen in the heart or BAT
• soleus muscle had a defect in state 3 (ADP-stimulated) mitochondrial respiration, but not state 2 (basal) or state 4 respiration
|
|
• weights of slow twitch fiber-enriched skeletal muscles, including gastrocnemius and soleus, but not the less oxidative tibialis anterior, were significantly lower at 3 and 8 weeks of age
|
|
• capacity to generate force following a series of tetani in soleus muscle was significantly lower in homozygous mutants, however there was no difference in force generation during the initial phase of stimulation, indicating muscle fatigability
|
nervous system
|
• observed areas of microvacuolation in multiple brainstem regions
|
|
• observed microvacuolation of the neuropil and neurons of the basal ganglia (caudate and putamen)
|
|
• the hippocampus showed neuronal microvacuolation
|
|
• observed patchy areas of microvacuolation involving the neuropil and individual pyramidal neurons of the deep layers of the cerebral cortex
|
|
• rare vacuolated Purkinje and granule cell neurons were identified in the cerebellar cortex
|
limbs/digits/tail
|
• weight of the gastrocnemius was significantly lower in 3 and 8 week old mutants
|
|
• weight of the soleus was significantly lower in 3 and 8 week old mutants
|
