CLONING AND CHARACTERIZATION OF THE MOUSE PIG-A GENE

Currently there is no experimental animal model for studying paroxysma l nocturnal hemoglobinuria (PNH), an acquired hemolytic anemia linked to mutations of the PIG-A gene. In this study, we cloned and character ized the mouse PIG-A gene. Sequencing of mouse PIG-A cDNA showed that it encodes a 485 amino acid-long protein. Northern hybridizations iden tified a major mRNA transcript of 3.6 kb and PCR amplifications identi fied four smaller alternative splice products. Exon:intron junctional analyses of the mouse PIG-A genome showed 6 exons (1(greater than or e qual to 60 bp), 2(780 bp), 3(133 bp) 4(133 bp), 5(207 bp), and 6(2276 bp)), the latter 5 of which encompass the coding region. Chromosomal m apping using C57BL/6J X M. Spretus backcross DNA localized the mouse P IG-A gene near the telomeric end of the mouse X chromosome. The isolat ion of the mouse PIG-A gene opens the possibility for the development of a mouse model of PNH.