title: Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae.
abstract: To address the expression and function of Hoxb13, the 5' most Hox gene in the HoxB cluster, we have generated mice with loss-of-function and beta-galactosidase reporter insertion alleles of this gene. Mice homozygous for Hoxb13 loss-of-function mutations show overgrowth in all major structures derived from the tail bud, including the developing secondary neural tube (SNT), the caudal spinal ganglia, and the caudal vertebrae. Using the beta-galactosidase reporter allele of Hoxb13, also a loss-of-function allele, we found that the expression patterns of Hoxb13 in the developing spinal cord and caudal mesoderm are closely associated with overgrowth phenotypes in the tails of homozygous mutant animals. These phenotypes can be explained by the observed increased cell proliferation and decreased levels of apoptosis within the tail of homozygous mutant mice. This analysis of Hoxb13 function suggests that this 5' Hox gene may act as an inhibitor of neuronal cell proliferation, an activator of apoptotic pathways in the SNT, and as a general repressor of growth in the caudal vertebrae.
authors.affiliation: Howard Hughes Medical Center, Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Kyriakos D
authors.initials: KD
authors.lastname: Economides
authors.forename: Lori
authors.initials: L
authors.lastname: Zeltser
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D005727:Ganglia, Spinal / Q000002:abnormalities; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation; D032446:Myoblasts / Q000502:physiology; D013116:Spinal Cord / Q000002:abnormalities / Q000196:embryology; D013131:Spine / Q000002:abnormalities / Q000196:embryology*; D013623:Tail / Q000002:abnormalities / Q000196:embryology*
chemical_list: D018398:Homeodomain Proteins; C100943:Hoxb13 protein, mouse