Localization of a Recessive Juvenile Cataract Mutation to Proximal Chromosome 7 in Mice

Abstract

Objective: To localize the chromosomal position of a novel cataract mutation (juvenile recessive cataract; jrc) in mice. Methods: A mapping population was developed by crossing cataract males (albino MH) to wild-type females (black C57BL/6J). F₁ females were backcrossed to albino MH males with cataracts. Results: The results were consistent with a model of a single autosomal recessive gene [153 cataract, 169 wild-type; χ² = 0.8, 1 degree of freedom (d.f.), p > 0.35]. Linkage with the albino (tyrosinase; Tyr) locus was evident (χ² = 61.5, 1 d.f., p < 0.0001), implicating chromosome 7 as the location of jrc. Recombination percentages (± SE) between jrc and D7Mit340 (1.2 cM location), D7Mit227 (16.0 cM) and D7Mit270 (18.0 cM) were 17.1 ± 2.1, 3.7 ± 1.1 and 6.2 ± 1.3%, respectively. Multi-point mapping determined that the most likely order of these loci is D7Mit340 – jrc – D7Mit227 – D7Mit270 – Tyr. Although animals with the mutant phenotype appeared to have little or no sense of sight, their growth was not different (p >0.20) from that of normal mice. Conclusion: The jrc mutation model may be useful in the study of the genetics of cataracts in other animal species, including humans.

A 16.7 kb deletion in Sipa1l3 is associated with juvenile cataract in mice

“…The albino line was derived from a mouse line selected for heat loss and originating from a four-way cross of outbred populations (NIH, ICR, CF-1, and CFW) (Cargill et al 2001). Ten breeding cages, with two females and one male assigned per cage, were used to produce subsequent generations with limited inbreeding.…”

“…Mouse models have been used extensively in genetic research of these conditions, with over 400 reported loci associated with cataract across different strains including spontaneous and chemically or radiation-induced mutations (http://www.informatics.jax.org/). A spontaneous recessive mutation influencing lens formation was identified in a mouse line selected for heat loss (Cargill et al 2001) with an original genetic base comprising of four outbred populations (Jones et al 1992;Nielsen et al 1997). Mice homozygous for the recessive allele exhibited complete cataracts at a juvenile age (Fig.…”

“…This mutation, called jrc for juvenile recessive cataract mutation, was found to be linked to a tyrosinase (Tyr) recessive allele located on MMU7 that caused albino coat color. The position of the jrc locus was originally mapped between D7Mit340 (4.63 Mb) and D7Mit227 (36.58 Mb) (Cargill et al 2001) with a follow-up by Poskochil (2004, Undergraduate Honors Thesis, personal communication) who suggested that D7Mit266 (28.3 Mb) was the closest marker to jrc. An unknown protein was found to be absent in both water-soluble and insoluble protein profiles of the mice with cataracts compared to normal mice (Tebbe 1999, Undergraduate Honors Thesis, personal communication).…”