THE BETA-1-INTEGRIN DISTAL PROMOTER IS DEVELOPMENTALLY-REGULATED IN TRANSGENIC MICE

Transgenic mice harbouring 5' flanking sequences of the human beta1 in tegrin gene linked to the Escherichia coli lacZ gene have been generat ed to examine spatial and temporal distribution of the promoter activi ty during development. Our previous data showed that this regulatory r egion is composed by two promoters, called distal and proximal, locate d closely on the human genome. To determine the role of each promoter region during development we generated transgenic mice using these two sequences linked to the lacZ reporter gene. Their analysis shows that these two sequences, as determined by in vitro studies, have differen t efficiencies in promoting transcription. Actually mice carrying the proximal promoter region exhibit a weak lacZ expression resulting in a n undetectable beta-galactosidase activity in both embryonic and adult tissues. On the other hand, transgenic mice carrying the distal promo ter express beta-galactosidase at high efficiency during embryonic dev elopment. The pattern of transgene expression is consistent with the l ocalization of beta1 protein on mouse embryos evidenced by immunohisto chemistry. Moreover the distal promoter is subjected to a temporal mod ulation since in adult transgenic mice lacZ expression decreases to a level detected only by RT-PCR analysis. We have determined a similar d own-regulation analysing by Northern blot beta1 mRNA in adult and embr yonic organs such as heart and gut.