Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation

Derrick E. Rancourt, Teruhisa Tsuzuki, Mario R. Capecchi

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Abstract

hoxb-5 and hoxb-6 are adjacent genes in the mouse HoxB locus and are members of the homeotic transcription factor complex that governs establishment of the mammalian body plan. To determine the roles of these genes during development, we generated mice with a targeted disruption in each gene. Three phenotypes affecting brachiocervicothoracic structures were found in the mutant mice. First, hoxb-5- homozygotes have a rostral shift of the shoulder girdle, analogous to what is seen in the human Sprengel anomaly. This suggests a role for hoxb-5 in specifying the position of limbs along the anteroposterior axis of the vertebrate body. Second, hoxb-6- homozygotes frequently have a missing first rib and a bifid second rib. The third phenotype, an anteriorizing homeotic transformation of the cervicothoracic vertebrae from C6 through T1, is common to both hoxb-5- and hoxb-6- homozygotes. Quite unexpectedly, hoxb-5, hoxb-6 transheterozygotes (hoxb-5- hoxb-6+/hoxb-5+ hoxb-6-) also show the third phenotype. By this classical genetic complementation test, these two mutations appear as alleles of the same gene. This phenomenon is termed nonallelic noncomplementation and suggests that these two genes function together to specify this region of the mammalian vertebral column.

Original languageEnglish
Pages (from-to)108-122
Number of pages15
JournalGenes and Development
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 1 1995

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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