MOLECULAR-GENETIC ANALYSIS OF DISTAL MOUSE CHROMOSOME-6 DEFINES GENE ORDER AND POSITIONS OF THE DEAFWADDLER AND OPISTHOTONOS MUTATIONS

Two neurological mutants deafwaddler (dfw) and opisthotonos (opt) and a cluster of three Shaker-like potassium (K) channel genes Kcna1, Kcna 5, and Kcna6 were all independently mapped to distal mouse chromosome six (Chr 6), In this study, genetic and molecular techniques were empl oyed to assess directly the linkage of the two mutants and to investig ate the likelihood that a mutation in one of the three K channel genes may underlie dfw, and/or opt. Genetic crosses testing for allelism sh owed that the dfw, and opt mutations complement each other, Additional crosses demonstrated that the mutants are separated by a recombinatio n distance of 3.1 +/- 1.8 cM. Microsatellite marker analysis of the cr ossover chromosomes recovered from the opt, dfw recombination study in dicated that opt maps centromeric to dfw. The location of the K channe l genes relative to the dfw mutation was determined by mapping these g enes and 15 microsatellite markers in an intersubspecific backcross (I B) segregating for dfw [(CAST/Ei-+/+ x C3HeB/FeJ-dfw/dfw) x C3HeB/FeJ- dfw/dfw]. Analysis of the backcross progeny positioned the dfw locus i n the interval between the microsatellite markers D6Mit11 and D6Mit55, D6Mit63. The K channel cluster maps telomeric to dfw. This study esta blishes the gene order cen-opt-dfw-Rho (D6Mit44)-Kcna1, Kcna5, Kcna6 o n distal mouse Chr 6 and suggests that the neurological mutants opt an d dfw affect two different genes, neither of which is caused by a muta tion in any one of the three clustered K channels. (C) 1995 Academic P ress, Inc.