We have analysed the transcriptional regulatory strategy of the rat tissue kallikrein gene family, a strategy that provides universal submandibular gland expression of all family members coupled with otherwise disparate expression of individual members in a wide variety of organs. To test whether a locus control region (LCR) or individual gene enhancers control the family, the expression patterns of rat kallikrein genes were examined in transgenic mice bearing a series of rat genomic fragments spanning the kallikrein locus. Each fragment, present in recombinant P1 phage clones, contained two or three linked members of the rat family. Rat (r) genes KLK1, KLK2, KLK3, KLK7, KLK8, KLK9 and KLK10 on four different P1 clones were all correctly expressed at high levels in the submandibular glands of transgenic mice and in general showed the correct extra-salivary patterns characteristic of each family member. Moreover, when the neighbouring family members rKLK1 and rKLK3 were separated on non-overlapping fragments and tested in mice, each transgene was expressed correctly in the submandibular gland and in other organs characteristic of that gene. Thus the family locus is not controlled by an LCR; rather each gene appears to have an associated transcriptional enhancer that specifies high submandibular expression and contributes to the additional organ specificity of the family member.
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