Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene.
Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain of mice carrying a disrupted Hoxa-5 allele. The viability of homozygous mutant mice is markedly reduced, with 50% of the mutant animals dying at birth or shortly thereafter. Analysis of the skeleton of Hoxa-5 mutants reveals a number of homeotic transformations restricted to the cervical and thoracic regions. Of these, one of the most frequent morphological abnormalities is the posterior transformation of the seventh cervical vertebra into the likeness of a thoracic vertebra complete with a pair of ribs. These results demonstrate that the Hoxa-5 gene has an important role in the establishment of the skeleton during development and contributes to the process whereby the axial structures are determined.
Jeannotte
L
L
Department of Genetics and Development, Columbia University, New York, New York 10032.
Lemieux
M
M
Charron
J
J
Poirier
F
F
Robertson
E J
EJ
D000818:Animals; D001755:Blastocyst / Q000502:physiology; D015139:Blotting, Southern; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000002:abnormalities / Q000033:anatomy & histology*; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005801:Genes, Homeobox; D005804:Genes, Lethal; D005838:Genotype; D018398:Homeodomain Proteins; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D004247:DNA