TISSUE-SPECIFIC EXPRESSION OF A FMR1 BETA-GALACTOSIDASE FUSION GENE IN TRANSGENIC MICE/

Fragile X syndrome is one of the most common genetic causes of mental retardation, yet the mechanisms controlling expression of the fragile X mental retardation gene FMR1 are poorly understood. To identify sequ ences regulating FMR1 transcription, transgenic mouse lines were estab lished using a fusion gene consisting of an E.coli beta-galactosidase reporter gene (lacZ) linked to a 2.8 kb fragment spanning the 5'-regio n of FMR1. Five transgenic mouse lines showed lacZ expression in brain , in particular in neurons of the hippocampus and the granular layer o f the cerebellum. Expression of the reporter gene was also detected in Leydig cells and spermatogonia in the testis, in many epithelia of ad ult mice, and in the two other steroidogenic cell types, adrenal corte x cells and ovarian follicle cells. Embryonic tissues which showed str ong activity of the reporter gene included the telencephalon, the geni tal ridge, and the notochord. This expression pattern closely resemble s the endogenous one, indicating that the 5' FMR1 gene promoter region used in this study contains most cis-acting elements regulating FMR1 transcription.