CLONING AND CHARACTERIZATION OF CDNAS AND THE GENE ENCODING THE MOUSEPLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE LB ALPHA-SUBUNIT LISSENCEPHALY-1 PROTEIN

Platelet-activating factor acetylhydrolases (PAFAHs) play an important role in the metabolism of PAF, a potent phospholipid mediator affecti ng various physiological processes. The heterotrimeric form of intrace llular PAF-AH consists of two catalytic subunits (PAF-AH Ib beta and P AF-AH Ib gamma) and a potential regulatory subunit (PAF-AH Ib alpha). Hemizygous deletion of the gene encoding the alpha subunit has been im plicated 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 Paf aha/Lis1 gene. We have cloned five cDNAs representing alternatively po lyadenylated messages. Northern blot analysis revealed that the variou s Pafaha/Lis1 mRNAs are differentially expressed in mouse tissues. The Pafaha/Lis1 gene spans a genomic region of more than 50 kb and consis ts of 12 exons, the first 2 of which are embedded in CpG islands. We h ave identified two sites of alternative splicing of Pafaha/Lis1: one a ffecting the length of the 5' untranslated region, the other potential ly resulting in a truncated form of the encoded protein. (C) 1998 Acad emic Press.