3 BRAIN SODIUM-CHANNEL ALPHA-SUBUNIT GENES ARE CLUSTERED ON THE PROXIMAL SEGMENT OF MOUSE CHROMOSOME-2

We have used long-range physical mapping and restriction fragment length polymorphisms between two mouse species to determine the chromosomal organization and location of the genes encoding three distinct isoforms of the α-subunit of the brain sodium channel. Physical mapping by pulsed-field gel electrophoresis has established that Scn2a and Scn3a (genes encoding type II and type III sodium channel α-subunit isoforms) are physically linked and are separated by a maximum distance of 600 kb. The segregation of restriction fragment length variations in backcross progeny of a Mus musculus and Mus spretus mating indicates that Scn1a (gene encoding the type I sodium channel α subunit) and Scn2a are tightly linked and are separated by a distance of 0.7 cM. Linkage analysis in backcross and recombinant inbred (BXD and AKXD) strains of mice localized the three sodium channel genes to the proximal segment of mouse chromosome 2 and suggested the probable gene order centromere-Hc-Neb-Pmv7-Scn2a/Scn3a-Scn1a-Mpmv14. These results indicate that the three isoforms of the brain sodium channel α-subunit are encoded by three distinct genes that share a common ancestral origin. © 1991.