Analysis Tools
behavior/neurological
polyphagia
(
J:148752
)
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• mice eat twice as much food as controls yet have the same bodyweight
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growth/size/body
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• mutants have decreased weight compared to controls at six months of age but not two (at 6 months, mean 36.8 g for wild-type versus 32.2 g for mutant)
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cellular
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• loss of oxidative intermediates in the urine leads to less circulating C2 acetylcarnitine due to increased use of acetyl-CoA in the TCA cycle
• this is further observed in the increased levels of serum ketones
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renal/urinary system
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• there are increases in excretion of short chain acetylcarnitines
• 3-methylhistidine excretion in the urine is twice that of controls indicative of increased proteolysis in skeletal muscle
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• crystals are present in the urine that consist of 60% tyrosine and 40% glutamine
• 16 amino acids are secreted at significantly increased levels in the urine
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• sodium levels in urine are significantly decreased (mean of 117 nM in wild-type versus 87 nm in controls)
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• mice are unable to concentrate urine to the same degree as controls after 18 hours of water deprivation (3,189 mosmol/kgH2O vs. 3880 mosmol/kgH2O)
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• urine urea levels are reduced by ~38% relative to those in wild-type controls
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crystalluria
(
J:148752
)
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• crystals present in urine consist of 60% tyrosine and 40% glutamine
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• mice have a greater urine output with a mean of 1.8 ml per day compared to 1.1 mls for controls
• this polyuria is secondary to an osmotic diuresis where mutant mice have higher osmotic clearance and free water absorption
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homeostasis/metabolism
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• there is a trend of lower levels of amino acids in skeletal muscle and in the liver
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• there is a 54% decrease in circulating levels of carnitine and similar decreases in short chain acetylcarnitines
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• levels of methionine are significantly increased in the serum
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• levels of tyrosine are significantly increased in the serum
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• mean serum ketone levels are at 500 nM compared to 300 nM in controls
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• 18 hours of water deprivation leads to a greater than 5-fold increase in serum sodium levels compared to similarly treated controls
• baseline (i.e. before water restriction) serum sodium levels are normal
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• insulin sensitivity in mice is increased at 6 months of age but not two compared to controls
• in glucose clearance tests, mutants have about 40% less circulating insulin than wild-type controls
• in insulin tolerance testing, mice have a greater drop in glucose from baseline than controls 30, 60, and 90 minutes after insulin injection
• mice also have a value that is almost one-third of controls in a homeostasis model assessment of insulin resistance derived from fasting glucose and fasting insulin levels
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• there are increases in excretion of short chain acetylcarnitines
• 3-methylhistidine excretion in the urine is twice that of controls indicative of increased proteolysis in skeletal muscle
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• crystals are present in the urine that consist of 60% tyrosine and 40% glutamine
• 16 amino acids are secreted at significantly increased levels in the urine
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• sodium levels in urine are significantly decreased (mean of 117 nM in wild-type versus 87 nm in controls)
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• mice are unable to concentrate urine to the same degree as controls after 18 hours of water deprivation (3,189 mosmol/kgH2O vs. 3880 mosmol/kgH2O)
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• urine urea levels are reduced by ~38% relative to those in wild-type controls
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crystalluria
(
J:148752
)
|
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• crystals present in urine consist of 60% tyrosine and 40% glutamine
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adipose tissue
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• mice at 6 months of age have 25% less body fat
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muscle
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• 3-methylhistidine excretion in the urine is twice that of controls indicative of increased proteolysis in skeletal muscle
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