Mouse Genome Informatics
hm
    Oattm1Dva/Oattm1Dva
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
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 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 Ámol/mmol creatinine vs <1 Ámol/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
• 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, rescued homozygotes exhibit a slight shortening of photoreceptor outer segments
• 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 Ámol/mmol creatinine vs <1 Ámol/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
OMIM IDRef(s)
Gyrate Atrophy of Choroid and Retina; GACR 258870 J:29269