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K.M. Robinson, J.R. Taube, N.A. Reed, M.K. Duncan; Role of ßB2-Crystallin in Fertility . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2136.
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Purpose: It is well established that α-crystallins are expressed in nonlens tissue and function as molecular chaperones. However, while the ß/γ crystallins are present in nonlens tissues, their non-refractive functions are unidentified. ßB2-crystallin is a major water-soluble protein found in the adult ocular lens and the mutation of this gene results in autosomal dominant cataract. While investigating mice homozygous for the Crybb2Phil mutation, we observed that they produce infrequent, small litters, in contrast to the background strain. Methods: Quantitative fertility tests and sperm function assays were performed to calculate differences between litter sizes, fecundity, sperm count and sperm motility of Swiss-Webster and Crybb2Phil homozygous mice. Furthermore, light microscopy and SEM were used to study morphological differences in sperm, testis and ovary. RT-PCR and western analysis were performed to determine the expression of ßB2-crystallin in reproductive tissues. Results: Swiss-Webster matings produced litters of 12.7 + 2.5 pups, and had a fecundity of 12.8 + 4.0 pups per 30 day period. However, Crybb2Phil homozygous males mated with Swiss-Webster females produced litters of 9.5 + 3.4 pups, and had a fecundity of 5.4 + 4.2 pups per 30 day period. Additionally, Crybb2Phil homozygous females mated with Swiss-Webster males resulted in litters of 7.9 + 2.0 pups, and had a fecundity of 4.4 + 4.0 pups per 30 day period. Preliminary sperm function assays suggest significant differences in sperm count and motility. However, SEM did not show any morphological differences in sperm structure. The ßB2-crystallin protein was detected in the ovaries of mice and sperm of mice, bulls and humans. The ßB2-crystallin mRNA was expressed in the ovary and testis of mice. Developmental RT-PCR of the testis reveals the presence of ßB2-crystallin mRNA at day 1 before spermatogenesis begins, with a large upregulation of expression between day 15 and 17 corresponding to the onset of meiosis. Conclusion: Both male and female Crybb2Phil homozygous mice are subfertile; and this subfertility is autosomal recessive. Thus, ßB2-crystallin is likely to be important for male and female fertility, and may play a role in sperm function.
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