Disease relevance of Crygd

• Lens opacity 12 (Lop12) is a semidominant mutation that results in an irregular nuclear lens opacity similar to the human Coppock cataract [1].
• Proteins with mutations at the C terminus demonstrated no significant chaperone-like activity, failing to confer thermotolerance on E. coli and demonstrating no significant inhibition of protein aggregation in either gamma-crystallin or reduced insulin B chain assays [2].

High impact information on Crygd

• The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster [3].
• We have injected this gene into nuclei of various mouse somatic cells. delta-Crystallin is totally absent from mammalian lenses in which it is replaced by gamma-crystallin, thus this xenogeneic injection system should allow us to study tissue-specific gene expression [4].
• In situ detection of beta-galactosidase in lenses of transgenic mice with a gamma-crystallin/lacZ gene [5].
• The eye lens of the Fraser mouse contains a dominantly inherited cataract with reduced amounts of seven distinct but homologous gamma crystallins encoded by a family of gamma-crystallin genes [6].
• Many dominant inherited cataracts in humans and mice have been shown to map within the gamma-crystallin gene cluster [7].

Biological context of Crygd

• Finally, a T-->A exchange in exon 2 of the gammaD-crystallin encoding gene (symbol: Crygd) was demonstrated to be causative for the cataract phenotype; this particular mutation is, therefore, referred to Crygo(Aey4) [8].
• The candidate genes (the Cryg gene cluster and the closely linked Cryba2 gene) were sequenced [9].
• A number of murine cataract mutations have been localized to chromosome 1 close to the gamma-crystallin gene cluster (Cryg) (Everett et al., 1994, Genomics 20: 429-434; Löster et al., 1994, Genomics 23: 240-242) [10].
• The mutation was mapped to Chromosome 1 by a genome-wide linkage making the six gamma-crystallin encoding genes and the closely linked betaA2-crystallin encoding gene to relevant candidate genes [8].
• During a large-scale ENU mutagenesis screen, a mouse mutant with a dominant cataract was detected and referred to as Aey4 [8].

Anatomical context of Crygd

• Gamma-crystallin genes are specifically expressed in the eye lens [11].
• DNAs from cow-hamster and cow-mouse somatic hybrid cells segregating bovine chromosomes have been analyzed by Southern blotting and hybridization with human fibronectin and gamma crystallin probes [12].
• An experiment showing lens induction in gamma-crystallin/GFP transgenic lens ectoderm when it is recombined with mouse optic vesicle demonstrates conservation of inducing signals from amphibians and mammals [13].
• Members of the gamma-crystallin family were expressed as red fluorescent protein (HcRed) tagged proteins in the rabbit kidney epithelial cell line RK13 [14].
• Synthesis of gamma crystallin by a cloned cell line from Nakano mouse lens [15].

Associations of Crygd with chemical compounds

• Sequence analysis of the in vivo-labeled gamma-crystallin polypeptides that cofocused isoelectrically with the hybrid-selected translation products established that the four cloned cDNAs were derived from mRNAs encoding gamma-crystallin polypeptides with similar NH2 termini [16].
• The genes for isocitrate dehydrogenase-1, fibronectin, and gamma-crystallin are syntenic in man, mouse, and cow [17].
• By contrast with the water-soluble fraction, the normal day 9 urea-soluble fraction was deficient in gamma-crystallin polypeptides and enriched in anodic components whose relative electrophoretic mobilities were similar to those reported previously for phosphorylated bovine alpha A-crystallin and several cytoskeletal polypeptides [18].
• The general cysteine protease inhibitor, E-64, blocked cataract formation and gamma-crystallin cleavage in alpha 3 (-/-) lenses [19].
• Sodium dodecyl sulfate (SDS) and non-SDS slab-gel electrophoresis of the soluble proteins from the cultured cell revealed protein bands identical in pattern to those of purified gamma crystallin [15].

Other interactions of Crygd

• It suggests that the cluster of gamma-crystallin encoding genes (Cryg) and the betaA2-crystallin encoding gene Cryba2 are excellent candidate genes [20].
• Two mutations occur at the same site in the Crygd and Cryge genes (Leu45-->Pro) [9].
• Three murine cataract mutants (Cat2) are defective in different gamma-crystallin genes [10].
• Using a systematic candidate gene approach to analyze the entire Cryg cluster, an A-->G transition was found in exon 2 of Cryga for the ENU-436 mutation and is designated Cryga1Neu [10].
• The map position of Cryg, near the eye lens obsolescence (Elo) locus, was confirmed by the discovery that the restriction fragment patterns of gamma crystallin sequences differed between strain C3H/HeJ and the congenic anophthalmic mutant strain, C3H.Elo [21].

Analytical, diagnostic and therapeutic context of Crygd

• The heterogeneity inherent among gamma-crystallins of the mouse lens was investigated by sequence analysis of three gamma-crystallin-specific cDNAs [22].
• METHODS: All six gamma-crystallin-encoding genes were amplified by polymerase chain reaction (PCR) from cDNA or genomic DNA and sequenced [23].
• Northern blots probed with cDNA specific for alpha-, beta- or gamma-crystallin genes suggested a reduced transcription of the gamma-crystallin genes [24].
• Regional localization of the fibronectin and gamma crystallin genes to mouse chromosome 1 by in situ hybridization [25].
• The detection of total gamma-crystallin protein in the retina was performed using an antibody to bovine lens gamma-crystallins, applied to protein extracts in immunoblot analysis and to cryostat sections of ocular tissues in immunofluorescence studies [26].

References