Peterfy_1998_Genomics_47_200

Platelet-activating factor acetylhydrolases (PAF-AHs) play an important role in the metabolism of PAF, a potent phospholipid mediator affecting various physiological processes. The heterotrimeric form of intracellular PAF-AH consists of two catalytic subunits (PAF-AH Ib beta and PAF-AH Ib gamma) and a potential regulatory subunit (PAF-AH Ib alpha). Hemizygous deletion of the gene encoding the alpha subunit has been implicated in two related neurological disorders: isolated lissencephaly sequence and Miller-Dieker syndrome. Here we report the isolation and characterization of mouse Pafaha/Lis1 cDNAs and the corresponding Pafaha/Lis1 gene. We have cloned five cDNAs representing alternatively polyadenylated messages. Northern blot analysis revealed that the various Pafaha/Lis1 mRNAs are differentially expressed in mouse tissues. The Pafaha/Lis1 gene spans a genomic region of more than 50 kb and consists of 12 exons, the first 2 of which are embedded in CpG islands. We have identified two sites of alternative splicing of Pafaha/Lis1: one affecting the length of the 5' untranslated region, the other potentially resulting in a truncated form of the encoded protein.