CRYGD Mouse
Description
CRYGD Protein Structure and Function
CRYGD is a 23.5 kDa protein comprising 174 amino acids, fused with a 23-residue His-tag in recombinant forms for experimental studies . It belongs to the β/γ-crystallin superfamily, characterized by Greek key motifs that stabilize lens fiber cells. Mutations in CRYGD disrupt protein solubility and tertiary structure, leading to aggregation and cataract formation .
Mouse Models of Crygd Mutations
Multiple spontaneous and induced Crygd mutations in mice have been documented:
These models show phenotypes mirroring human congenital cataracts, such as bilateral nuclear opacities and vision loss .
Biochemical and Molecular Insights
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Aggregation Propensity: Mutant CRYGD (e.g., p.Trp43Arg, p.Arg36Ser) exhibits reduced solubility and increased aggregation under stress (heat/UV), disrupting lens transparency .
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Structural Instability: Missense mutations (e.g., p.Ser78Phe, p.Pro23Ser) alter conserved residues in Greek key motifs, destabilizing protein folding .
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Subcellular Mislocalization: Frameshift mutations (e.g., p.Tyr151*) lead to nuclear mislocalization in vitro, contrasting with wild-type CRYGD’s cytoplasmic distribution .
Comparative Analysis with Human Cataracts
Over 20 CRYGD mutations are linked to human cataracts, including:
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p.Trp43Arg: Causes autosomal dominant congenital nuclear cataracts via structural destabilization .
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p.Arg58His: Enhances crystallization propensity, forming lens deposits .
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p.Ser78Phe: A novel mutation disrupting conserved serine residues, reported in Chinese pedigrees .
Mouse models recapitulate these molecular pathologies, validating their utility for translational research .
Therapeutic Implications
Studies on Crygd mutants highlight strategies to enhance crystallin solubility, such as chemical chaperones or gene editing. For example, stabilizing CRYGD’s tertiary structure via compensatory mutations (e.g., reciprocal domain substitutions) shows promise in restoring lens clarity .
Product Specs
Gamma-crystallin D, Gamma-D-crystallin , Gamma-crystallin 1, CRYGD.
MGSSHHHHHH SSGLVPRGSH MGSMGKITFY EDRGFQGRHY ECSTDHSNLQ PYFSRCNSVR VDSGCWMLYE QPNFTGCQYF LRRGDYPDYQ QWMGFSDSVR SCRLIPHAGS HRIRLYEREE YRGQMIEFTE DCPSLQDRFH FNEIYSLNVL EGCWVLYDMT NYRGRQYLLR PGEYRRYHDW
GAMNARVGSL RRVMDFY
Product Science Overview
Crystallins are a family of proteins that are primarily found in the vertebrate eye lens, where they play a crucial role in maintaining the transparency and refractive index of the lens. Among the various types of crystallins, gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins that are typically devoid of connecting peptides and terminal extensions .
Gamma-crystallin D (CRYGD) is one of the four gamma-crystallin genes (gamma-A through gamma-D) that are organized in a gene cluster. In mice, the CRYGD gene is located on chromosome 1 . The protein encoded by this gene is involved in maintaining the optical properties of the lens by ensuring its transparency and refractive power .
The mouse recombinant CRYGD protein is produced in E. coli and consists of a single, non-glycosylated polypeptide chain containing 197 amino acids (1-174 a.a.) with a molecular mass of 23.5 kDa. It is fused to a 23 amino acid His-tag at the N-terminus and purified using proprietary chromatographic techniques .
Crystallins, including gamma-crystallins, are extremely stable proteins that are retained throughout the life of the lens cells. This stability is essential because lens central fiber cells lose their nuclei during development and do not produce or degrade proteins . The high concentration of crystallins in the lens helps to maintain its transparency and refractive index, which are critical for proper vision .
Gamma-crystallins, including CRYGD, have been implicated in cataract formation. Cataracts are characterized by the clouding of the lens, which leads to a decrease in vision. This condition is often associated with the aggregation of crystallin proteins due to aging or mutations in specific genes . Understanding the structure and function of gamma-crystallins can provide insights into the mechanisms underlying cataract formation and potential therapeutic approaches.
