| First Author | Chang B | Year | 2024 |
| Mgi Jnum | J:348118 | Mgi Id | MGI:7639999 |
| Citation | Chang B (2024) The eyeless 7 mutation (eyl7) in mice. |
| abstractText | The Rpe65tm1Tmr allele was generated in (129X1/SvJ x 129S1/Sv)F1 derived R1 ES cells by Dr. T. Michael Redmond, Ph.D., Molecular Mechanisms Section, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH. The eyeless 7 mutation (eyl7), which causes microphthalmia, arose spontaneously in that Rpe65tm1Tmr colony. Rpe65tm1Tmr homozygotes on the 129 background did not display the retinal white spots that are found in Rpe65rd12 homozygotes on a C57BL/6J background so a C57BL/6J congenic Rpe65tm1Tmr strain was generated for direct comparison. To do this, male mice homozygous for both Rpe65tm1Tmr and eyl7 were sent to The Jackson Laboratory in November 2012 and an importation IVF was done using oocytes from C57BL/6J. The obligate heterozygous F1 pups from the IVF had no abnormal phenotype, as expected, but the F2 population included approximately 25% of mice with the eyl7 microphthalmia (Figure 1A), and 25% with just the Rpe65tm1Tmr homozygous phenotype (Figure 1B). The mice with the microphthalmia phenotype in the F2 generation had an agouti coat color and a subline of mice with this mutation was generated by sibling inbreeding. This strain, B6;129-eyl7/Boc, was fixed homozygous for eyl7, but may also have still carried Rpe65tm1Tmr on Chromosome 3. Since all F1 mice had normal eyes and the microphthalmia phenotype occurred in approximately 25% of both female and male mice in the F2 generation, the microphthalmia was determined to be an autosomal recessive mutation. Linkage crosses with DBA/2J mapped the microphthalmia mutation to mouse Chromosome 19 and the best candidate gene in the region is Pitx3. Mutations in Pitx3 cause variable defects in many aspects of ocular development, including microphthalmia or anophthalmia, as well as other neurological defects and developmental defects elsewhere in the body (Rosemann M., et al., 2010). To generate the congenic strain B6.129-Rpe65tm1Tmr/Boc (Jax Stock Number: 035329) the mice with normal sized eyes (Figure 1B) in the F2 generation were tested by ERG at 1 month of age and a mouse with the retinal degeneration phenotype (caused by Rpe65tm1Tmr) but without microphthalmia was further backcrossed to C57BL/6J and subsequent generations of backcross-intercross breeding was done until the strain reached generation N6. This strain was compared with mice homozygous for the Rpe65rd12 mutation on the C57BL/6J background and the white retinal spots were evident in Rpe65tm1Tmr homozygotes on the C57BL/6J congenic background by 3 months of age (Figure 2 A and B), proving that genetic background impacts this aspect of the phenotype. |
