High-resolution linkage map in the vicinity of the Lp locus

Looptail (Lp) is a mutation that profoundly affects neurulation in mouse and is characterized by craniorachischisis, an open neural tube extending from the midbrain to the tail in embryos homozygous for the mutation. Lp maps to the distal portion of mouse chromosome 1, and as part of a positional cloning approach, we have generated a high-resolution linkage map of the Lp chromosomal region. For this, we have carried out extensive segregation analysis in a total of 706 backcross mice informative for Lp and derived from two crosses, (Lp/+ x SJL/J)F1 x SJL/J and (Lp/+ x SWR/J) F1 x SWR/J. In addition, 269 mice from a (Mus spretus x C57BL/6J)F1 x C57BL/6J interspecific backcross were also used to order marker loci and calculate intergene distances for this region. With these mice, a total of 28 DNA markers corresponding to either cloned genes or anonymous markers of the SSLP or SSCP-types were mapped within a 5-cM interval overlapping the Lp region, with the following locus order and interlocus distances (in cM): centromere--D1Mit110/Atp1 beta 1/Cd3 zeta/Cd3 eta/D1Mit145-D1Hun14/D1Mit15- D1Mit111/D1Mit112-D1Mit114-D1Mit148/D1Mit205+ ++/D1Mit36/D1Mit146/D1Mit147/D1Mit270 / D1Hun13-Fcgr2-Mpp-Apoa2/Fcer1 gamma-Lp-D1Mit149/Spna1/Fcer1 alpha-Eph1-Hlix1/D1Mit62. These studies have allowed the delineation of a maximum genetic interval for Lp of 0.5 cM, a size amenable to physical mapping techniques.