Analysis Tools
mortality/aging
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• although born at expected Mendelian ratios, >50% of mice die by P7 and all mice are dead at P10
• attempts to decrease the litter size at P3 or compensate malnutrition by s.c. administration of an AA-containing solution fail to increase lifespan
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embryo
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• at E18, fetuses show low amniotic fluid AAs, suggesting impaired transplacental transport
• defective fetal AA delivery is not restricted to Slc43a2-specific substrates but includes most AAs
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growth/size/body
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• pups gain significantly less weight from P5 to P9 relative to controls
• feeding behavior is normal, as evidenced by the presence of a milk spot
• attempts to decrease the litter size or compensate malnutrition fail to increase weight gain
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• at E18, fetuses show a ~10% weight reduction relative to controls
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• fetuses exhibit a slight intrauterine growth retardation relative to wild-type and heterozygous controls
• however, no additional obvious phenotypes are observed
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homeostasis/metabolism
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• after 30 min of starvation followed by oral administration of a radiolabeled AA solution, mice show a 2-fold increase in the retention of labeled L-leucine (a Slc43a2 substrate), but not of L-lysine, in the proximal part of the small intestine relative to wild-type controls
• however, no differences in L-leucine levels are observed in plasma or other organs (liver, kidney and heart)
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• at P3, plasma levels of certain non-essential AAs that are not substrates of Slc43a2 are significantly decreased
• proline shows the highest reduction (~75%) followed by histidine, serine and alanine
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• at P3, mice show a trend towards increased plasma levels of long-chain unsaturated acylcarnitines; in particular, C18:1 is significantly increased
• plasma dicarboxylacylcarnitines (DAs) levels are significantly increased
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• proline shows the highest reduction (~75%) in plasma
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• mice killed at P2 show highly variable blood glucose levels relative to controls
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• after 30 min of starvation, all pups sacrificed at P2 show a ~50% reduction in blood glucose levels relative to controls
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• at E18, fetuses show a >50% reduction in the concentration of almost all AAs in the amniotic fluid, with the exception of aspartate and glutamate
• however, glucose and total protein concentration and osmolarity are normal
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• at P3, mice show an increase of plasma acylcarnitine-conjugated fatty acids, esp. dicarboxylic acids and long-chain unsaturated fatty acids, suggesting malnutrition
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digestive/alimentary system
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• after 30 min of starvation followed by oral administration of a radiolabeled AA solution, mice show a 2-fold increase in the retention of labeled L-leucine (a Slc43a2 substrate), but not of L-lysine, in the proximal part of the small intestine relative to wild-type controls
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liver/biliary system
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• gene expression analysis suggested major metabolic alterations, inflammation, toxicity and regeneration at the level of the liver
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• at P2, mice show sites of leucocyte infiltration in the periportal region of the liver
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immune system
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• at P2, mice show sites of leucocyte infiltration in the periportal region of the liver
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