title: ENU-induced allele of brachyury (Tkt1) exhibits a developmental lethal phenotype similar to the original brachyury (T) mutation.
abstract: New alleles of brachyury (Tkt1, Tkt4) were induced in the mouse complete tw5 haplotype by ethylnitrosourea (ENU). Like the original brachyury (T) mutation, the new alleles cause a short-tailed phenotype in heterozygotes, and interact with the t complex tail interaction factor (tct) in trans to cause phenotypically tailless mice. Because ENU is mainly a point mutagen, it is important to determine that the new alleles are homozygous embryonic lethal mutations like the original T allele, and to characterize their embryonic lethal phenotype. Moreover, the Tkt1 mutation maps to an inverted position relative to quaking (qk) in t haplotypes as compared with its position on normal chromosome 17. The Tkt1 allele was separated from the resident tw5 lethal gene, tclw5, by recombination, allowing embryology studies to be performed. Embryological analyses show that the Tkt1 allele is nearly identical to the classic T allele. At 9 and 10 days of development, homozygous Tkt1/Tkt1 embryos are grossly abnormal with properties including 1) irregular, disorganized somite pairs, 2) a shortened posterior end of the embryo, 3) an irregular neural tube, and 4) an abnormal notochord. In addition, 10 day-old abnormal embryos have anterior limb buds that point dorsally rather than ventrally, and are smaller than normal littermates. We conclude that the Tkt1 mutation is a valuable allele for both mapping and molecular characterization of the brachyury locus.
authors.affiliation: Division of Biology, Kansas State University, Manhattan 66506.
authors.forename: M J
authors.initials: MJ
authors.lastname: Justice
authors.forename: V C
authors.initials: VC
authors.lastname: Bode
mesh_terms: D000483:Alleles; D000818:Animals; D016009:Chi-Square Distribution; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000002:abnormalities*; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D005804:Genes, Lethal; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009153:Mutagens; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic
chemical_list: D009153:Mutagens; D005038:Ethylnitrosourea