Identification of a new chemically induced allele (Lp(m1Jus)) at the loop-tail locus: morphology, histology, and genetic mapping.

Loop-tail (Lp) is a semidominant mutation that affects neurulation in mice. Heterozygous animals are characterized by a looped-tail appearance (pig tail) and wobbly head movements while homozygous embryos exhibit a neural tube closure defect that extends from the caudal midbrain to the tip of the tail. The Lp gene has been finely mapped to the distal part of chromosome 1, and a positional cloning strategy has been initiated to isolate the defective gene. This study represents the characterization of a new Lp allele (Lp(m1Jus)) induced by N-ethyl-N-nitrosurea mutagenesis. Lp(m1Jus)/+ mice have a looped-tail appearance, and both Lp(m1Jus)/Lp(m1Jus) homozygotes and Lp/Lp(m1Jus) compound heterozygotes fail to initiate neural tube closure along most of the embryonic axis. These data indicate that the Lp(m1Jus) allele causes a neural tube defect and overall phenotype similar to that of the original Lp allele. Segregation analysis of 90 (Lp(m1Jus)/+ x C57BL/6J)F(1) x C57BL/6J looped-tail mice with seven markers that define the Lp genetic map (D1Mit455/D1Mit146/D1Mit148/D1Mit270-1 cM-D1Mit113-0.4 cM-Lp-0.2 cM-D1Mit149-0.8 cM-D1Mit115) showed significant linkage between Lp(m1Jus) and all loci analyzed (P < 0.0001). Eight crossovers were detected with the proximal cluster of D1Mit455, D1Mit146, D1Mit148, and D1Mit270, indicating a recombination rate higher than expected in this region, and a single recombinant was encountered with the distal markers D1Mit149 and D1Mit115. Based on these phenotypic and genetic data, Lp(m1Jus) is most likely allelic to Lp, thereby representing a valuable additional tool for the positional cloning of the Lp gene and its subsequent molecular characterization.