Cell-specific and Developmental Regulation of a Nerve Growth Factor-human Growth Hormone Fusion Gene in Transgenic Mice

We recently showed that a nerve growth factor-human growth hormone (NGF-hGH) fusion gene containing the promoter and 750 bp of 5' flanking region is transcriptionally active in the NGF-secreting L929 mouse fibroblast cell line. For the present experiments, we extended the 5' flank by 5 kb and constructed transgenic mice. These mice began to secrete hGH into saliva at puberty. hGH was detected immunocytochemically in the granulated convoluted tubular cells of the submandibular gland (SMG). SMG levels of hGH mRNA were 10-fold higher in adult males than in females. hGH mRNA was very abundant in SMG, moderately abundant in heart, brain, and kidney, rare in skin and adrenal gland, and undetectable in lung, liver, and spleen. Thus, the NGF-hGH gene reflects NGF gene expression. We conclude that basal NGF gene transcription is regulated by sequences in the cloned NGF gene fragment.