TISSUE-SPECIFIC IN-VIVO TRANSCRIPTION START SITES OF THE HUMAN AND MURINE CYSTIC-FIBROSIS GENES

The in vivo transcription start sites of the human cystic fibrosis tra nsmembrane conductance regulator gene (CFTR) and its murine homologue (Cftr) have been mapped in a range of tissues using the technique of 5 ' rapid amplification of cDNA ends (5' RACE), These are the first in v ivo transcription start sites for CFTR or Cftr to be reported, Distinc t, tissue-specific patterns of CFTR start site usage were identified i n both mouse and human, In particular, striking variation in the posit ion of the murine Cftr transcription start site was seen along the len gth of the intestinal tract; different start sites being utilized in i leum and in duodenum, In humans, distinct transcription start sites ar e utilized in adult and foetal lungs. In addition, a novel 5'-untransl ated exon of murine Cftr, denoted exon -1, was identified and shown to be expressed exclusively in mouse testis, Expression of exon -1-conta ining Cftr transcripts was shown by mRNA in situ hybridization to be c onfined to the germ cells and to be regulated during spermatogenesis.