Phenotypes associated with this allele

• Allele Symbol: Oat^tm1Dva
• Allele Name: targeted mutation 1, David Valle
• Allele ID: MGI:2150441
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Oat^tm1Dva/Oat^tm1Dva	involves: 129S7/SvEvBrd	MGI:3719126
hm2	Oat^tm1Dva/Oat^tm1Dva	involves: 129S7/SvEvBrd * C57BL/6J	MGI:2174900
ht3	Oat^rhg/Oat^tm1Dva	involves: 129S7/SvEvBrd * AKR/J * C57BL/6J * C57BL/6JEi	MGI:6162527

Genotype
MGI:3719126

hm1

• Allelic Composition: Oat^tm1Dva/Oat^tm1Dva
• Genetic Background: involves: 129S7/SvEvBrd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Retinal histopathology of Oat^tm1Dva/Oat^tm1Dva mice

homeostasis/metabolism

abnormal circulating amino acid level ( J:60200 )

• mutants that have been rescued with arginine supplementation for the first two weeks of life and then placed on a standard chow diet, exhibit a 13-fold increase in plasma ornithine levels and mean plasma lysine that is about 50% of controls

• mutants placed on an arginine-restricted diet after the arginine rescue have normal plasma amino acid levels

vision/eye

abnormal retina morphology ( J:60200 )

disorganized photoreceptor inner segment ( J:60200 )

• photoreceptor inner segments are highly disorganized in mutants on a standard diet

short photoreceptor inner segment ( J:60200 )

• photoreceptor inner segments are shortened in mutants on a standard diet

absent photoreceptor outer segment ( J:60200 )

• photoreceptor outer segments are virtually absent in mutants on a standard diet

abnormal retina pigment epithelium morphology ( J:60200 )

• in mutants on a standard diet, most retinal pigment epithelium (RPE) cells lose their basal infoldings and have greatly reduced apical microvilli, some are swollen and engorged with lipid inclusions, others contain clusters of small electron dense granules with the fine structure of glycogen

thin retina outer nuclear layer ( J:60200 )

• the outer nuclear layer is reduced to 2-3 layers of nuclei, instead of the normal 9-10 layers, in mutants on a standard diet

retina degeneration ( J:60200 )

• mutants on a standard diet after the initial arginine supplementation exhibit severe retinal degeneration

• however, mutants placed on an arginine-restricted diet exhibit normal retinas

abnormal eye electrophysiology ( J:60200 )

• mutants on a standard diet with hyperornithinemia exhibit a gradual reduction in ERG amplitude beginning at around 4 months of age

• however, mutants on an arginine-restricted diet that have near normal levels of ornithine plasma levels have normal ERG amplitudes

pigmentation

abnormal retina pigment epithelium morphology ( J:60200 )

• in mutants on a standard diet, most retinal pigment epithelium (RPE) cells lose their basal infoldings and have greatly reduced apical microvilli, some are swollen and engorged with lipid inclusions, others contain clusters of small electron dense granules with the fine structure of glycogen

nervous system

disorganized photoreceptor inner segment ( J:60200 )

• photoreceptor inner segments are highly disorganized in mutants on a standard diet

short photoreceptor inner segment ( J:60200 )

• photoreceptor inner segments are shortened in mutants on a standard diet

absent photoreceptor outer segment ( J:60200 )

• photoreceptor outer segments are virtually absent in mutants on a standard diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
gyrate atrophy		DOID:1415	OMIM:258870	J:60200

Genotype
MGI:2174900

hm2

• Allelic Composition: Oat^tm1Dva/Oat^tm1Dva
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

neonatal lethality, complete penetrance ( J:29269 )

• 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

abnormal circulating amino acid level ( J:29269 )

• 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

decreased circulating arginine level ( J:29269 )

• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma arginine concentrations

decreased circulating citrulline level ( J:29269 )

• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma citrulline concentrations

decreased circulating ornithine level ( J:29269 )

• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma ornithine concentrations

increased circulating ornithine level ( J:29269 )

• in contrast to neonates, post-weaning (adult) homozygotes on a standard diet exhibit severe hyperornithinemia

decreased circulating phenylalanine level ( J:29269 )

• pre-weaning (neonatal) homozygotes that have been rescued with arginine supplementation show a significant reduction in plasma phenylalanine concentrations

increased circulating ammonia level ( J:29269 )

• pre-weaning homozygotes that have been rescued with arginine supplementation exhibit a 5-fold increase in blood ammonia levels relative to wild-type mice

oroticaciduria ( J:29269 )

• 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

decreased retina photoreceptor cell number ( J:29269 )

• at 7 months or later, rescued homozygotes exhibit a moderate (20-30%) photoreceptor loss relative to wild-type mice

short photoreceptor outer segment ( J:29269 )

• 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

abnormal retina pigment epithelium morphology ( J:29269 )

• 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

retina degeneration ( J:29269 )

• post-weaning (adult) homozygotes exhibit slow retinal degeneration

renal/urinary system

oroticaciduria ( J:29269 )

• 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

lethargy ( J:29269 )

• newborn homozygotes cease feeding and become lethargic within a few hours after birth

nervous system

decreased retina photoreceptor cell number ( J:29269 )

• at 7 months or later, rescued homozygotes exhibit a moderate (20-30%) photoreceptor loss relative to wild-type mice

short photoreceptor outer segment ( J:29269 )

• 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

abnormal retina pigment epithelium morphology ( J:29269 )

• 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

Genotype
MGI:6162527

ht3

• Allelic Composition: Oat^rhg/Oat^tm1Dva
• Genetic Background: involves: 129S7/SvEvBrd * AKR/J * C57BL/6J * C57BL/6JEi

integument

retarded hair growth ( J:213842 )

growth/size/body

decreased body size ( J:213842 )

• delayed growth by 7 days of age, which can be ameliorated by i.p. injection of arginine

nervous system

short photoreceptor outer segment ( J:213842 )

• somewhat shortened and disorganized at 12 months of age

homeostasis/metabolism

increased circulating ornithine level ( J:213842 )

• plasma ornithine is increased to approximately 1200 uM

pigmentation

retina pigment epithelium atrophy ( J:213842 )

mortality/aging

preweaning lethality, incomplete penetrance ( J:213842 )

• only 70% of compound heterozygotes survive to weaning without arginine supplementation, and 45% of compound heterozygotes die before one year

vision/eye

short photoreceptor outer segment ( J:213842 )

• somewhat shortened and disorganized at 12 months of age

retina pigment epithelium atrophy ( J:213842 )