Crygc-flox Mouse

Crygc, encoding γC-crystallin protein, is crucial for maintaining lens transparency. Crystallins are the major structural proteins in the eye lens, and their proper function is essential for clear vision. Mutations in Crygc are associated with congenital cataract, a significant cause of childhood blindness and amblyopia [1,3,4,5,6,7,8,9,10].

In mouse models, a dominant mutation in Crygc that causes cataracts could be rescued by coinjecting Cas9 mRNA and a single-guide RNA (sgRNA) targeting the mutant allele into zygotes. Correction occurred via homology-directed repair (HDR), based on an exogenously supplied oligonucleotide or the endogenous WT allele, demonstrating the potential of CRISPR-Cas9 system in correcting genetic diseases related to Crygc [2].

In human studies, various mutations in Crygc have been identified. For example, a de novo missense mutation at c.391T>C in exon 3 of CRYGC causes the substitution of a highly conserved tryptophan to an arginine (p.Trp131Arg), which can lead to changes in the tertiary structure of the crystallin family, making it prone to aggregation and resulting in cataract [1]. Another study identified a heterozygous frameshift mutation c.389_390insGCTG (p.C130fs) in a Chinese family with autosomal dominant congenital cataracts and microcornea [3].

In conclusion, Crygc is vital for maintaining lens transparency, and its mutations are closely associated with congenital cataract. Mouse models, especially those utilizing gene-editing techniques like CRISPR-Cas9, have provided valuable insights into the role of Crygc in cataract-related diseases, offering potential directions for genetic diagnosis and treatment.