Cloning and Characterization of cDNAs and the Gene Encoding the Mouse Platelet-Activating Factor Acetylhydrolase Ib α Subunit/Lissencephaly-1 Protein

Abstract

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 Ibβ and PAF-AH Ibγ) and a potential regulatory subunit (PAF-AH Ibα). Hemizygous deletion of the gene encoding the α subunit has been implicated in two related neurological disorders: isolated lissencephaly sequence and Miller–Dieker syndrome. Here we report the isolation and characterization of mousePafaha/Lis1cDNAs and the correspondingPafaha/Lis1gene. We have cloned five cDNAs representing alternatively polyadenylated messages. Northern blot analysis revealed that the variousPafaha/Lis1mRNAs are differentially expressed in mouse tissues. ThePafaha/Lis1gene 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 ofPafaha/Lis1: one affecting the length of the 5′ untranslated region, the other potentially resulting in a truncated form of the encoded protein.