PMID- 8620844
OWN - NLM
STAT- MEDLINE
DCOM- 19960617
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 122
IP  - 4
DP  - 1996 Apr
TI  - A mutational analysis of the 5' HoxD genes: dissection of genetic interactions 
      during limb development in the mouse.
PG  - 1175-85
AB  - Using gene targeting in mice, we have undertaken a systematic mutational analysis 
      of the homeobox-containing 5' HoxD genes. In particular, we have characterized 
      the limb defects observed in mice with independent targeted disruptions of 
      hoxd-12 and hoxd-13. Animals defective for hoxd-12 are viable, fertile, and 
      appear outwardly normal yet have minor autopodal defects in the forelimb which 
      include a reduction in the bone length of metacarpals and phalanges, and a 
      malformation of the distal carpal bone d4. The limb phenotypes observed in 
      hoxd-13 mutant mice are more extensive, including strong reductions in length, 
      complete absences, or improper segmentations of many metacarpal and phalangeal 
      bones. Additionally, the d4 carpal bone is not properly formed and often produces 
      an extra rudimentary digit. To examine the genetic interactions between the 5' 
      HoxD genes, we bred these mutant strains with each other and with our previously 
      characterized hoxd-11 mouse to produce a series of trans-heterozygotes. Skeletal 
      analyses of these mice reveal that these genes interact in the formation of the 
      vertebrate limb, since the trans-heterozygotes display phenotypes not present in 
      the individual heterozygotes, including more severe carpal, metacarpal and 
      phalangeal defects. Some of these phenotypes appear to be accounted for by a 
      delay in the ossification events in the autopod, which lead to either the failure 
      of fusion or the elimination of cartilaginous elements. Characteristically, these 
      mutations lead to the overall truncation of digits II and V on the forelimb. 
      Additionally, some trans-animals show the growth of an extra postaxial digit VI, 
      which is composed of a bony element resembling a phalange. The results 
      demonstrate that these genes interact in the formation of the limb. In addition 
      to the previously characterized paralogous interactions, a multitude of 
      interactions between Hox genes is used to finely sculpt the forelimb. The 5' Hox 
      genes could therefore act as a major permissive genetic milieu that has been 
      exploited by evolutionary adaptation to form the tetrapod limbs.
FAU - Davis, A P
AU  - Davis AP
AD  - Howard Hughes Medical Institute, Department of Human Genetics, University of Utah 
      School of Medicine, Salt Lake City 84112, USA.
FAU - Capecchi, M R
AU  - Capecchi MR
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (HOXD13 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxd13 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Carpal Bones/growth & development
MH  - Crosses, Genetic
MH  - Forelimb/*growth & development
MH  - Gene Expression
MH  - Gene Targeting
MH  - Genes, Homeobox/*physiology
MH  - Heterozygote
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Metacarpus/growth & development
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Phenotype
MH  - Toes/growth & development
MH  - *Transcription Factors
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - 10.1242/dev.122.4.1175 [doi]
PST - ppublish
SO  - Development. 1996 Apr;122(4):1175-85. doi: 10.1242/dev.122.4.1175.