STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF THE RAT NEUROTROPHIN-4 GENE

Neurotrophin-4 (NT-4) is a member of the neurotrophin family of growth factors. To study the molecular mechanisms that govern NT-4 expressio n, we have cloned and characterized the rat genome region encoding NT- 4. The rat NT-4 gene consists of three exons: two 5'-flanking noncodin g exons and a coding exon. NT-4 mRNA transcription is controlled by tw o promoters flanking the noncoding exons. Alternative splicing of the second intron results in a NT-4 mRNA with a different open reading fra me, encoding a shorter protein lacking pre-NT-4 sequence. A rat NT-4 g ene fragment, containing all exons and introns in addition to 1.4 kb o f the upstream genomic sequence, has been introduced into mice. This t ransgene enables partial recapitulation of the expression pattern of N T-4 mRNA and confers activity-dependent expression of the NT-4 mRNA in muscle.