Analysis Tools
mortality/aging
|
• although apparently normal at birth, all homozygotes die 24-48 hrs after birth
• i.p. administration of L-arginine (10 mmol/kg body weight every 12 hrs, starting within hrs after birth and reduced to 2 mmol/kg/injection over the first 14 days of life) extends survival to 80%; arginine is no longer required for viability after day 14
• premature cessation of arginine treatment causes lethargy, prostate posture, rigidity, and the onset of a resting, high frequency tremor in the distal extremities and tail, culminating to death within a few hrs of birth; a single i.p. dose of arginine shortly after the onset of symptoms restores normal posture and activity within 1-3 hrs
|
homeostasis/metabolism
|
• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a 20-40% reduction in several amino acids (e.g. phenylalanine), with significant reductions in plasma ornithine, arginine, and citrulline concentrations
• in contrast to neonates, post-weaning (adult) homozygotes on a standard diet exhibit severe hyperornithinemia and hypolysinemia, similar to humans with gyrate atrophy
|
|
• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma arginine concentrations
|
|
• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma citrulline concentrations
|
|
• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma ornithine concentrations
|
|
• in contrast to neonates, post-weaning (adult) homozygotes on a standard diet exhibit severe hyperornithinemia
|
|
• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma phenylalanine concentrations
|
|
• pre-weaning homozygotes that have been rescued with arginine supplementation exhibit a 5-fold increase in blood ammonia levels relative to wild-type mice
|
|
• pre-weaning homozygotes that have been rescued with arginine supplementation exhibit severe orotic aciduria with 145 76 mol/mmol creatinine vs <1 mol/mmol in wild-type mice
|
vision/eye
|
• at 7 months or later, rescued homozygotes exhibit a moderate (20-30%) photoreceptor loss relative to wild-type mice
|
|
• at 2 months, rescued homozygotes exhibit a slight shortening of photoreceptor outer segments
• by 7 months or later, mutant photoreceptor outer segments appear disorganized and markedly shortened, esp. in the central superior and inferior retinal regions
|
|
• at 2 months, mutant retinas display normal morphology with slight swelling of the RPE
• by 7 months or later, mutant RPE cells exhibit irregular swelling and doming and some have migrated into the outer segment layer
|
|
• post-weaning (adult) homozygotes exhibit slow retinal degeneration
|
renal/urinary system
|
• pre-weaning homozygotes that have been rescued with arginine supplementation exhibit severe orotic aciduria with 145 76 mol/mmol creatinine vs <1 mol/mmol in wild-type mice
|
behavior/neurological
|
• newborn homozygotes cease feeding and become lethargic within a few hours after birth
|
nervous system
|
• at 7 months or later, rescued homozygotes exhibit a moderate (20-30%) photoreceptor loss relative to wild-type mice
|
|
• at 2 months, rescued homozygotes exhibit a slight shortening of photoreceptor outer segments
• by 7 months or later, mutant photoreceptor outer segments appear disorganized and markedly shortened, esp. in the central superior and inferior retinal regions
|
pigmentation
|
• at 2 months, mutant retinas display normal morphology with slight swelling of the RPE
• by 7 months or later, mutant RPE cells exhibit irregular swelling and doming and some have migrated into the outer segment layer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| gyrate atrophy | DOID:1415 |
OMIM:258870 |
J:29269 | |
