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Publication : The mouse beta B1-crystallin promoter: strict regulation of lens fiber cell specificity.

First Author  Chen WV Year  2001
Journal  Biochim Biophys Acta Volume  1519
Issue  1-2 Pages  30-8
PubMed ID  11406268 Mgi Jnum  J:70057
Mgi Id  MGI:2136127 Doi  10.1016/s0167-4781(01)00201-9
Citation  Chen WV, et al. (2001) The mouse beta B1-crystallin promoter: strict regulation of lens fiber cell specificity. Biochim Biophys Acta 1519(1-2):30-8
abstractText  Previous studies have shown that the chicken beta B1-crystallin promoter (-434/+30) contains all of the signals necessary to specifically direct high level expression of heterologous genes to the lens fiber cells of mice. In the present study, the mouse beta B1-crystallin gene was cloned, and its regulation was investigated to further elucidate the mechanisms controlling lens fiber cell-specific gene expression. Phylogenetic footprinting analysis of the 5' flanking sequence from the mouse, rat, human and chicken beta B1-crystallin genes identified several known and putative functional cis elements including the PL2 element which is required for lens-specific expression of the chicken beta B1 promoter. Surprisingly, however, all six mouse beta B1-crystallin/CAT constructs tested (-1493/+44, -1493/+30, -870/+30, -250/+30, -135/+30 and -98/+30) were inactive in three different mammalian lens-derived cell lines while only the -870/+30 and -98/+30 constructs were active in chicken primary patched lens epithelial cells. In contrast, the chicken beta B1-crystallin promoter (-434/+30) was transcriptionally active in all lens-derived cells tested. Transgenic mice harboring a mouse beta B1-crystallin -1493/+44 CAT construct did express the transgene specifically in lens fiber cells, however, at lower levels than that previously reported for a chicken -434/+30 CAT construct. These data suggest that, as in other crystallin genes, the regulatory signals controlling lens fiber cell-specific expression are conserved between chicken and mouse. However, the inability of the mouse beta B1-crystallin promoter to function in mammalian lens-derived cultured cells implies that this gene has acquired additional cis-regulatory elements to ensure lens fiber cell specificity.
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