STRUCTURE OF THE HUMAN LAMININ GAMMA-2 CHAIN GENE (LAMC2) - ALTERNATIVE SPLICING WITH DIFFERENT TISSUE DISTRIBUTION OF 2 TRANSCRIPTS

We have determined the structure of the human laminin gamma 2 chain ge ne (LAMC2), which is mutated in some patients with junctional epidermo lysis bullosa. Eight lambda phage clones isolated from a genomic libra ry and three subgenomic lambda phage clones made from a plasmid artifi cial chromosome clone spanned 75 kb, including the 55-kb gene. The LAM C2 gene contains 23 exons and is structurally highly homologous with t he 28-exon LAMC1 gene (Kallunki et al., 1991, J. Biol. Chem. 266: 221- 228), with 16 exons having identical sizes in the two genes. The gene analysis demonstrated that two previously described different size gam ma 2 chain cDNAs (Kallunki et al., 1992, J. Cell Biol. 119: 679-693) a re the result of alternative splicing. The longer gamma 2 chain is for med by using the coding sequence of the last exon 23, while the shorte r gamma 2 chain is formed by using only 22 exons, together with part of the 5' end of intron 22. The two mRNAs were shown to have different expression patterns in 17-week-old human embryonic tissues, with the longer gamma 2 chain transcript strongly expressed in epithelia of all tissues studied, while distinct expression of the shorter gamma 2 ch ain mRNA was observed only in the cerebral cortex, in lung, and in dis tal tubules of the kidney. (C) 1996 Academic Press, Inc.