mortality/aging
• when citrulline supplement was withdrawn from one mouse it died within 15 days
• one female died 3 hours after delivery
• however, the one mouse maintained on a citrulline supplemented diet survived without disease for 25 months
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• fewer than expected mice are born
• while pup cannibalization is observed, fostering after birth does not improve lethality nor does supplementing dam diets with citrulline or arginine
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• 16 of 18 mice die within 24 hours of birth
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reproductive system
• one female had a single pregnancy after several unsuccessful matings that ended on day 18 with pups being cannabilized by the mother
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embryo
• at E16.5, mice exhibit developmental delay of 2 to 3 days
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• at E16.5
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growth/size/body
• at E16.5, mice exhibit developmental delay of 2 to 3 days
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• at E16.5
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• at birth, mice are smaller and less vital than wild-type mice
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weight loss
(
J:125847
)
• when citrulline was withdrawn the mouse lost 63% of its initial weight
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• despite being supplemented with citrulline, the two surviving mice exhibited lasting growth retardation
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• 240 mg in male and 220 mg in female compared to 102+/-5 mg in wild-type mice
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behavior/neurological
• one female exhibited nonresponsiveness to external stimuli 3 hours after delivery
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• when citrulline was withdrawn the one mouse developed tremors
• one female exhibited tremors 3 hours after delivery
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• one female had a single pregnancy after several unsuccessful matings that ended on day 18 with pups being cannabilized by the mother
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homeostasis/metabolism
• whether or not two mice were low protein fed a diet supplemented with citrulline, mice excrete excess arginine, ornithine and orotic acid
• one male on a citrulline-supplemented normal diet excreted excess lysine
• however, E16.5 amniotic fluid cationic amino acid levels are normal
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• 1050 umol/L in male and 1530 umol/L in female compared to 135.5+/-40.8 umol/L in wild-type mice and 137.3+/-24.7 umol/L in heterozygous mice
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hematopoietic system
• 240 mg in male and 220 mg in female compared to 102+/-5 mg in wild-type mice
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muscle
• when citrulline was withdrawn the one mouse developed hypotonia
• one female exhibited severe hypotonia 3 hours after delivery
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skeleton
• bone development is delayed
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renal/urinary system
• whether or not two mice were low protein fed a diet supplemented with citrulline, mice excrete excess arginine, ornithine and orotic acid
• one male on a citrulline-supplemented normal diet excreted excess lysine
• however, E16.5 amniotic fluid cationic amino acid levels are normal
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immune system
• 240 mg in male and 220 mg in female compared to 102+/-5 mg in wild-type mice
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