B6(A)-Crygc^M2J/BocJ

Stock number: 039039
Research areas: Developmental Biology Research, Sensorineural Research

Description

This semi-dominant spontaneous 5 nucleotide duplication after the third Greek key motif of crystallin gamma C causes lens fiber cell defects, defective mineralization in the lens, severe early cataracts in homozygotes and milder cataracts later in life in heterozygotes.

Detailed description

This semi-dominant spontaneous 5 nucleotide duplication after the third Greek key motif is predicted to result in a frameshift, translation of a stretch of aberrant sequence, and premature termination before the fourth Greek key motif. At 10 days of age homozygous lens fiber cells in the nuclear region are variable in size, shape and organization and show some failed denucleation. Decreased levels and aberrant staining of lens alphaA and betaB1 crystallins, GJA3, and GJA8 are found, there is a scarcity of gap junctions between lens fiber cells, lenses have decreased gap junctional conductance, and calcium phosphate, in the form of apatite, is found in the lenses. As a result, homozygotes develop severe nuclear cataracts, by approximately wean age, with multiple small opacities distributed in a shamrock-like formation between the cortex and nucleus. Heterozygotes, which also have some failed denucleation of the lens fiber cells but lack the severe mineralization in the lens, develop much more mild nuclear cataracts encircled by a halo much later in life, starting around 2 to 3 months of age, with the number and size of these nuclear opacities progressing with age.

Development

The Crygb^S11R mutation arose spontaneously in A/J. The Crygc^M2J mutation arose spontaneously during the backcrossing of Crygb^S11R from A/J to C57BL/6J. That backcross tracked the phenotype of cataract, which both mutations cause, and the Crygb^S11R mutation was lost and the Crygc^M2J mutation arose during the backcrossing. The cryopreserved bankstock was found to have Crygc^M2J and lack Crygb^S11R, which is now extinct.

Allele

Symbol: Crygc^M2J
Name: mutation 2 Jackson
MGI accession ID: MGI:7549103
Generation method: Spontaneous
Attributes: Hypomorph
Synonyms: Crygc^dup
Marker symbol: Crygc
Marker name: crystallin, gamma C
Marker synonyms: CCL; Cryg; CRYG3; Cryg-5; CTRCT2; Len
Chromosome: 1
Strain of origin: B6.A-Crygb^S11R/BocJ
Molecular note: This spontaneous 5bp duplication, c.409_413dup, is predicted to result in a frameshift after the third greek key motif, translation of a stretch of aberrant sequence, and premature termination before the fourth greek key motif