C57BL/6J-Aipl1^tvrm119/PjnMmjax

Stock number: 031246
Product name: tvrm119
Research areas: Sensorineural Research

Description

This ENU-induced point mutation, tvrm119, occurs in the splice donor site of Aipl1 and is predicted to lead to a loss of exon 2 - thereby yielding a protein lacking much of the FK506 binding protein homology domain. Homozygotes provide a model for Leber congenital amaurosis 4/early-onset cone-rod dystrophy/juvenile retinitis pigmentosa. Homozygotes for this allele have a later onset than homozygotes for the Aipl1^tvrm127 allele (see MMRRC Stock No. 043594).

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, tvrm119, causes early onset photoreceptor degeneration in homozygotes. The fundus appears grainy with attenuated blood vessels and patchy retina. Mice homozygous for the tvrm119 allele of Aipl1 have a less severe rate of onset of photoreceptor degeneration than Aipl1^tvrm127 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 - an 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 tvrm127 and not 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 - an age when 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 has been identified as a nucleotide substitution (c.276++5 G>A)in a splice donor site of Aipl1 (aryl hydrocarbon receptor-interacting protein-like 1). The mutation is predicted to lead to a loss of exon 2 - resulting in an in-frame deletion of amino acids Val33-Ile92. The deletion includes much of the FKBP homology domain.

Allele

Symbol: Aipl1^tvrm119
Name: translational vision research model 119
MGI accession ID: MGI:5810589
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 c.276+5G>A single nucleotide transition in a splice donor site is predicted to delete expression of exon 2 and thereby result in an in-frame deletion of amino acids Val33-Ile92, which includes much of the FKBP homology domain.