Crygs, the gene encoding gamma-S crystallin, is a crucial gene as gamma-S crystallin is one of the major structural proteins in the eye lens, playing a vital role in maintaining lens transparency [2,3,4]. It is also expressed in non-lens tissues like the retina and cornea in some species, suggesting additional non-crystallin roles, perhaps related to stress response [4].

In mice, a mutation in Crygs causes the Opj cataract. The Opj mutation replaces Phe-9 with serine, leading to a temperature-sensitive phenotype where the mutant protein folds normally at low temperature but has reduced solubility and loss of secondary structure near physiological temperatures. This is similar to processes in human senile cataracts. In Opj/Opj mice, cortical fiber cell morphology and the loss of maturing fiber cell nuclei are severely disrupted, indicating a loss of gamma-S crystallin function related to maintaining cytoarchitecture [2]. In a Chinese family, a novel heterozygous missense mutation c.199T > A, p.(Tyr67Asn) in CRYGS was identified, which was predicted to decrease local hydrophobicity, affect the three-dimensional structure of γS-crystallin, and cause partial mutant protein translocation from the cytoplasm to the cell membrane, resulting in congenital cataract [1]. A G18V mutation in human gammaS-crystallin associated with autosomal dominant cortical progressive cataract makes the protein more sensitive to thermal and chemical stress, which is consistent with the progressive cataract formation in family members carrying this mutation [3].

In conclusion, Crygs is essential for maintaining the normal structure and function of the eye lens. Studies on mouse models with Crygs mutations, like the Opj cataract model, have revealed its role in preventing cataract formation. Understanding the function of Crygs through these models provides insights into the molecular mechanisms of cataractogenesis, which may contribute to the development of strategies for cataract prevention and treatment.