C57BL/6J-Aipl1^tvrm127/PjnMmjax

Stock number: 031250
Product name: tvrm127
Research areas: Sensorineural Research

Description

This ENU-induced point mutation, tvrm127, occurs in the splice donor site of the Aipl1 gene and is predicted to lead to a cysteine to phenylalanine substitution at amino acid 89 (C89F), which is predicted to disrupt farnesyl-Cys binding as is found in a human Cys89Arg allele. Homozygotes provide a model for Leber congenital amaurosis 4/early-onset cone-rod dystrophy/juvenile retinitis pigmentosa. Homozygotes for this allele have an earlier onset than homozygotes for the Aipl1^tvrm119 (MMRRC Stock 043590) allele.

Detailed description

AIPL1 (aryl hydrocarbon receptor-interacting protein-like 1) consists of an N-terminal FK506 binding protein (FKBP) domain and three tetratricopeptide motifs and is expressed in the retina and pineal gland. Mutations in Aipl1 are associated with Leber congenital amaurosis (LCA). This Aipl1 point mutation, tvrm127 causes early onset photoreceptor degeneration in homozygotes. The fundus appears grainy with attenuated blood vessels and patchy retina. Mice homozygous for the tvrm127 allele of Aipl1 have a faster rate of onset of photoreceptor degeneration than Aipl1^tvrm119 homozygotes. Although both homozygotes and their compound heterozygotes undergo degeneration that leaves only one layer of photoreceptor nuclei by 1 month of age, Aipl1^tvrm119 homozygotes have normal outer segment lengths and 9 to 10 layers of photoreceptor nuclei at 12 days of age, when Aipl1^tvrm127 homozygotes already have outer segment shortening and only 7 layers of photoreceptor nuclei. At 12 days of age, both homozygotes have a reduction in retinal PDE6A, and mislocalization of rhodopsin to the outer nuclear layer, but Aipl1^tvrm127 and not Aipl1^tvrm119 homozygotes have cone sheaths displaced throughout the outer nuclear layer at this stage, and at 18 days of age Aipl1^tvrm119 homozygotes have a reduced amplitude in dark-adapted ERG responses, when Aipl1^tvrm127 homozygotes have no dark-adapted ERG response.

Development

This mutation was generated in C57BL/6J and has remained coisogenic on this background. The ENU treated male was bred to a C57BL/6J female, their offspring were intercrossed and their female offspring were backcrossed to their father to generate third generation mutants likely to express recessive phenotypes. After screening identified this eye mutation backcrossing was done to C57BL/6J to remove any additional unlinked mutations. The mutation was identified as a G to T substitution at nucleotide 266 of the Aipl1 (aryl hydrocarbon receptor-interacting protein-like 1) gene, resulting in a cysteine to phenylalanine substitution at amino acid 89 (C89F).

Allele

Symbol: Aipl1^tvrm127
Name: translational vision research model 127
MGI accession ID: MGI:5810590
Generation method: Chemically induced (ENU)
Attributes: Not Specified
Marker symbol: Aipl1
Marker name: aryl hydrocarbon receptor-interacting protein-like 1
Marker synonyms: A930007I01Rik; AIPL2; LCA4
Chromosome: 11
Strain of origin: C57BL/6J
Molecular note: This ENU-induced G to T transversion at nucleotide 266 is predicted to lead to a Cys89Phe amino acid substitution at amino acid 89 (C89F).