title: Rescue of the neural tube defect of loop-tail mice by a BAC clone containing the Ltap gene.
abstract: The mouse mutant loop-tail (Lp) is an accepted model for the study of neural tube defects (NTDs) in humans. Whereas Lp/+ heterozygotes show a mild tail defect (looped), homozygous Lp/Lp embryos show a very severe form of NTD, with a completely open neural tube from the hindbrain region to the caudal portion of the spinal cord (craniorachischisis). We have recently identified a positional candidate for Lp on chromosome 1, designated as Ltap. Here, we have used an in vivo complementation approach in transgenic mice to attempt to correct the looped-tail phenotype with a bacterial artificial chromosome clone (BAC280A23) that harbors a full-length copy of the Ltap gene. Genotype:phenotype correlations in Lp/+ heterozygotes carrying BAC280A23 show that this clone can rescue the looped-tail phenotype in two independent founder lines (P < 0.05 and P < 0.0001). Importantly, BAC280A23 is also observed to rescue the lethal NTD of Lp/Lp homozygotes, because several viable transgenic Lp/Lp mice could be identified and appeared normal (P < 0.05). Results from these gain-of-function transgenic animals strongly suggest that the positional candidate Ltap present in this BAC is indeed the gene that is defective in loop-tail.
authors.affiliation: Department of Biochemistry, McGill Cancer Center, Center for the Study of Host Resistance, McGill University, Montreal, QC, Canada H3G-1Y6.
authors.forename: Zoha
authors.initials: Z
authors.lastname: Kibar
authors.forename: Susan
authors.initials: S
authors.lastname: Gauthier
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidal
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism
chemical_list: C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins