Transcription mapping and expression analysis of candidate genes in the vicinity of the mouse Loop-tail mutation

Loop-tail (Lp) is a semidominant mutation that maps to the distal portion o f mouse Chromosome (Chr) 1 and is an established model for neural tube defe cts (NTDs). Homozygous em bryos exhibit an open neural tube from the caudal midbrain to the tip of the tail that results from over-differentiation of the floor plate. To facilitate the positional cloning of the Lp gene, both cDNB selection and assignment of sequence-tagged-sites from the human trans cript map have been used to identify genes within the Lp interval. Together with previous physical mapping, this has allowed the placement of 13 trans cription units within an approximately 1-Mb region that spans the Lp geneti c interval, and eight of these genes map to the nonrecombinant interval. Th is map includes genes that encode proteins involved in protein sorting and targeting (Tim23 and Copa), ion transport (Atp1a2, Atp1a4, and Girk3), tran scription (Nhlh1), immune regulation (Cd48 and Fcer1 alpha). cell adhesion (R88252), apoptosis (Pea15), and several of unknown function (H326, Kiaa025 3, and Estm34). Expression analysis by Northern blotting indicated that a s ubset of these genes are expressed preferentially in the developing nervous system. Finally this region of mouse Chr 1 represents a conserved linkage group with genes on human chromosome 1q21, a region that is frequently alte red in human cancers and that harbors loci for several genetic conditions. Consequently, analysis of the Lp interval may provide important tools to un derstand how the corresponding region of human Chr 1 contributes to disease , in addition to defining a key gene product required for neurulation.