The genomic organization of type I keratin genes in mice

We isolated two new keratin cDNAs by screening a cDNA library constructed f rom poly(A)(+) RNA of the dorsal and abdominal skin of C57BL/10J mice with a probe of human KRT14 Due to its high sequence homology to human keratin 1 7 cDNA, one full-length cDNA is most likely to be mouse keratin 17 (Krt1-17 ) cDNA. The other is the putative full-length cDNA of a novel type I kerati n gene, designated Krt1-c29. These two keratin genes were mapped to the dis tal portion of Chromosome 11, where the mouse keratin gene complex-1 (Krt1) is localized. To elucidate the genomic organization of Krt1 in mice, we ca rried out genetic and physical analyses of Krt1. A large-scale linkage anal ysis using intersubspecific backcrosses suggested that there are two major clusters in Krt1, one containing Krt1-c29, Krt1-10, and Krt1-12 and the oth er containing Krt1-14, -15, -17, and -19. Truncation experiments with two y east artificial chromosome clones containing the two clusters above have re vealed that the gene order of Ki tl is centromere-Krt1-c29-Krt1-10-Krt1-12- Krt1-13-Krt1-15-Krt1-19-Krt1-14-Krt-17-telomere. Finally, we analyzed seque nce divergence between the genes belonging to the Krtl complex. The results clearly indicated that genes are classified into two major groups with res pect to phylogenetic relationship. Each group consists of the respective ge ne cluster demonstrated by genetic and physical analyses in this study, sug gesting that the physical organization of the Krt1 complex reflects the evo lutionary process of gene duplication of this complex. (C) 1999 Academic Pr ess.