Cloning and characterization of the mouse PIG-A gene

Currently there is no experimental animal model for studying paroxysmal nocturnal hemoglobinuria (PNH), an acquired hemolytic anemia linked to mutations of the PIG-A gene. In this study, we cloned and characterized the mouse PIG-A gene. Sequencing of mouse PIG-A cDNA showed that it encodes a 485 amino acid-long protein. Northern hybridizations identified a major mRNA transcript of 3.6 kb and PCR amplifications identified four smaller alternative splice products. Exon:intron junctional analyses of the mouse PIG-A genome showed 6 exons (1(> or = 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 mapping using C57BL/6J x M. Spretus backcross DNA localized the mouse PIG-A gene near the telomeric end of the mouse X chromosome. The isolation of the mouse PIG-A gene opens the possibility for the development of a mouse model of PNH.