Disease relevance of Cryaa

• Mutations in the alphaA-crystallin-encoding gene Cryaa lead to recessive and dominant cataracts [1].
• We have shown by site-directed mutagenesis that the sequence between positions -69 and -40 of the mouse alpha A-crystallin gene is crucial for tissue-specific gene expression in a transfected mouse lens epithelial cell line transformed with the early region of simian virus 40 [2].
• Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain [3].
• Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin) [3].
• Demyelination and axonal dystrophy in alpha A-crystallin transgenic mice [4].

High impact information on Cryaa

• Alternative RNA splicing of the murine alpha A-crystallin gene: protein-coding information within an intron [5].
• The phenotype of this engineered developmental mutation suggests that the normal development of alpha A-crystallin-producing lens fiber cells is essential for the proper growth, organization, and orientation of optic structures [6].
• A chimeric gene was formed by fusing the promoter and 5'-flanking sequences of the lens-specific mouse alpha A-crystallin gene with a modified ricin A cDNA, and this construction was integrated into the germ line of transgenic mice [6].
• Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin [7].
• These data, coupled with our recent demonstration that Pax-6 activates the alpha A-crystallin gene, suggest that Pax-6 may have been used extensively throughout evolution to recruit and express crystallin genes in the lens [8].

Chemical compound and disease context of Cryaa

• Transgenic mice were generated carrying either the long terminal repeat of Human Immunodeficiency Virus fused to the bacterial chloramphenicol acetyl transferase reporter gene or a control element of the murine alpha A crystallin gene fused to the tat gene of human immunodeficiency virus [9].

Biological context of Cryaa

• Stimulation of alpha A-crystallin promoter activity via 8-bromo-cAMP, forskolin, or human T-cell leukemia virus type I Tax1 in transfections and reduction of activity of this site in cell-free transcription tests by competition with the somatostatin CRE supported the idea that DE1 is a functional CRE [10].
• Using the fibre cell-specific alpha A-crystallin promoter to express the FGFRDN, we have asked whether FGF is required for fibre cell differentiation [11].
• There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains [12].
• The alpha-A-crystallin and cystathionine beta-synthase genes are physically very closely linked in proximal mouse chromosome 17 [13].
• We have used a complementary DNA (cDNA) for mouse alpha A-crystallin to probe genomic DNA for restriction fragment length polymorphisms which could be used to map the alpha A-crystallin gene locus (Acry-1) in the mouse genome [14].

Anatomical context of Cryaa

• Finally, Pax-6, a member of the paired-box family of transcription factors, activated the mouse alpha A-crystallin promoter in cotransfected COP-8 fibroblasts and bound to the -59 to -29 promoter sequence in EMSAs [10].
• 5. During subsequent development of the lens, alpha A crystallin transcripts are most abundant in the fiber cells, and alpha B crystallin mRNA is preferentially expressed in epithelial cells [15].
• The bovine eye lens protein alpha A-crystallin has been overexpressed both by stable transfection of HeLa cells and by transient transfection of NIH 3T3 cells [16].
• Our experiments thus demonstrate that the explanted embryonic chicken lens epithelium is an advantageous recipient for identifying lens-cell-specific regulatory sequences of crystallin genes and implicate a DNA region upstream of the "TATA box" for regulation of the murine alpha A-crystallin gene [17].
• The putative control region of the mouse alpha A-crystallin gene was footprinted by DNase I digestion in nuclear extracts, by dimethylsulfate treatment in cultured cells, and by micrococcal nuclease digestion in isolated nuclei [18].

Associations of Cryaa with chemical compounds

• Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site [10].
• Lens-specific expression of the chloramphenicol acetyltransferase gene promoted by 5' flanking sequences of the murine alpha A-crystallin gene in explanted chicken lens epithelia [17].

Physical interactions of Cryaa

• A partial cDNA with sequence similarity to alpha A-CRYPB1 of the mouse has been isolated from a chicken lens library; mouse alpha A-CRYBP1 is a putative transcription factor which binds to the -66/-55 sequence of the mouse alpha A-crystallin promoter.(ABSTRACT TRUNCATED AT 250 WORDS)[19]

Regulatory relationships of Cryaa

• alpha A-crystallin binding protein I (alpha A-CRYBP1) is a ubiquitously expressed DNA binding protein that was previously identified by its ability to interact with a functionally important sequence in the mouse alpha A-crystallin gene promoter [20].

Other interactions of Cryaa

• CONCLUSIONS: Transcription of alpha B-crystallin precedes the expression of alpha A-crystallin during murine ocular development [15].
• The expression pattern of Pax2 appeared normal; Cryaa expression could not be detected [21].
• In addition, we also tested the same collection of t haplotypes for their variability at five D17Leh, Hba-ps4, Pim-1, and Crya-1 loci [22].
• The locus encoding alpha A-crystallin is closely linked to H-2K on mouse chromosome 17 [14].
• Linkage analysis was conducted on DNA from three sets of recombinant inbred strains of mice and demonstrated close linkage of Acry-1 with the major histocompatibility complex (H-2) on chromosome 17 [14].

Analytical, diagnostic and therapeutic context of Cryaa

• Sequence analysis revealed a mutation of a T to an A at position 371 in the Cryaa cDNA [23].
• Genomic footprinting, in vitro footprinting and mobility shift assays were used to investigate the molecular basis for expression of mouse alpha A-crystallin, a major structural protein of the transparent lens of vertebrates [18].
• Binding of tissue-specific forms of alpha A-CRYBP1 to their regulatory sequence in the mouse alpha A-crystallin-encoding gene: double-label immunoblotting of UV-crosslinked complexes [24].
• METHODS: The technique of in situ hybridization was applied using a probe from the murine gamma D-crystallin gene, and, for control, from the murine alpha A-crystallin gene [25].
• Previously, we assigned the alpha A2-crystallin (Crya-1) structural gene to mouse chromosome 17 via Southern blot hybridization analysis of mouse x Chinese hamster somatic cell hybrids [26].

References