Homozygotes develop severe nuclear cataracts evident by 7 days of age, but not at birth, and heterozygotes display a hazy nuclear cataract at wean age. Toluidine blue staining of the lens at 3 days of age shows uneven stain of the inner lens fiber cells with darkly stained areas in both heterozygotes and homozygotes and disintegrated fiber cells in homozygotes. The peripheral lens fiber cells, even at 3 weeks of age, appear morphologically normal and the periphery of mutant lenses is transparent even in older homozygotes. In newborn homozygotes gamma crystalline aggregates are found adjacent to the cell boundary of inner fiber cells in a manner segregated from F-actin. Actin filaments disappear from inner fiber cells beginning at approximately 220 um from the lens capsule at 7 days of age and extending to 350 um from the lens capsule by 21 days of age. As a result, a ring-like structure is found approximately 220 to 350 um from the lens capsule that causes light scattering. Western blotting shows cleaved forms of alphaB and gamma crystallins at 7 days of age and alphaA, alphaB, beta and gamma crystallins at 21 days of age in mutant but not wild-type lenses, with more cleaved crystallins in homozygotes than heterozygotes and no cleaved crystallins found in the lenses at birth. Inductively coupled plasma-optical emission spectrometry performed to assess lens ion concentration at 10 days of age showed an approximately 4-fold increase in calcium concentration in homozygotes, and a lesser increase in heterozygotes.
The S11R mutation in Crygb arose spontaneously in the A/J inbred strain at The Jackson Laboratory in approximately 2000. This mutation was backcrossed onto the C57BL/6J background in the laboratory of Dr. Bo Chang. Sperm was cryopreserved from homozygous males.
|Gene Symbol and Name||Crygb, crystallin, gamma B|
|Strain of Origin||A/J|
|Molecular Note||A T-to-G (A-to-C on negative gene strand) point mutation in codon 11 results in the substitution of serine with arginine at position 11 (p.S11R).|