TY - JOUR
T1 - Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional redundancy and regulatory interactions
AU - Branford, William W.
AU - Benson, Gail V.
AU - Ma, Liang
AU - Maas, Richard L.
AU - Potter, S. Steven
N1 - Funding Information:
We thank Professors Peter Gruss and Denis Duboule for the HoxA and HoxD riboprobe constructs, respectively. This work was supported by NIH Grant HD32061 to S.S.P, by NIH Grant HD35580 to R.L.M., and by NIH-NRSA Grant HD08264 to L.M. We thank Shaun Heaney and Yueyun Ding for technical help and Dr. Hyunjung Lim for critically reading the manuscript.
PY - 2000/8/15
Y1 - 2000/8/15
N2 - Hox genes show related sequences and overlapping expression domains that often reflect functional redundancy as well as a common evolutionary origin. To accurately define their functions, it has become necessary to compare phenotypes of mice with single and multiple Hox gene mutations. Here, we focus on two Abd-B-type genes, Hoxa-10 and Hoxa-11, which are coexpressed in developing vertebrae, limbs, and reproductive tracts. To assess possible functional redundancy between these two genes, Hoxa-10/Hoxa-11 transheterozygotes were produced by genetic intercrosses and analyzed. This compound mutation resulted in synergistic defects in transheterozygous limbs and reproductive tracts, but not in vertebrae. In the forelimb, distal radial/ulnar thickening and pisiform/triangular carpal fusion were observed in 35 and 21% of transheterozygotes, respectively, but were effectively absent in Hoxa-10 and Hoxa-11 +/- forelimbs. In the hindlimb, distal tibial/fibular thickening and loss of tibial/fibular fusion were observed in >80% of transheterozygotes but in no Hoxa-10 or Hoxa-11 +/- hindlimbs, and all transheterozygotes displayed reduced medial patellar sesamoids, compared to modest incidences in Hoxa-10 and Hoxa-11 +/- mutants. Furthermore, while the reproductive tracts of Hoxa-10 and Hoxa-11 single heterozygous mutants of both sexes were primarily unaffected, male transheterozygotes displayed cryptorchidism and abnormal tortuosity of the ductus deferens, and female transheterozygotes exhibited abnormal uterotubal junctions and narrowing of the uterus. In addition we observed that the targeted mutations of Hoxa-10 and Hoxa-11 each affected the expression of the other gene in the developing prevertebra and reproductive tracts. These results provide a measure of the functional redundancy of Hoxa-10 and Hoxa-11 and a deeper understanding of the phenotypes resulting in the single mutants and help elucidate the regulatory interactions between these two genes. (C) 2000 Academic Press.
AB - Hox genes show related sequences and overlapping expression domains that often reflect functional redundancy as well as a common evolutionary origin. To accurately define their functions, it has become necessary to compare phenotypes of mice with single and multiple Hox gene mutations. Here, we focus on two Abd-B-type genes, Hoxa-10 and Hoxa-11, which are coexpressed in developing vertebrae, limbs, and reproductive tracts. To assess possible functional redundancy between these two genes, Hoxa-10/Hoxa-11 transheterozygotes were produced by genetic intercrosses and analyzed. This compound mutation resulted in synergistic defects in transheterozygous limbs and reproductive tracts, but not in vertebrae. In the forelimb, distal radial/ulnar thickening and pisiform/triangular carpal fusion were observed in 35 and 21% of transheterozygotes, respectively, but were effectively absent in Hoxa-10 and Hoxa-11 +/- forelimbs. In the hindlimb, distal tibial/fibular thickening and loss of tibial/fibular fusion were observed in >80% of transheterozygotes but in no Hoxa-10 or Hoxa-11 +/- hindlimbs, and all transheterozygotes displayed reduced medial patellar sesamoids, compared to modest incidences in Hoxa-10 and Hoxa-11 +/- mutants. Furthermore, while the reproductive tracts of Hoxa-10 and Hoxa-11 single heterozygous mutants of both sexes were primarily unaffected, male transheterozygotes displayed cryptorchidism and abnormal tortuosity of the ductus deferens, and female transheterozygotes exhibited abnormal uterotubal junctions and narrowing of the uterus. In addition we observed that the targeted mutations of Hoxa-10 and Hoxa-11 each affected the expression of the other gene in the developing prevertebra and reproductive tracts. These results provide a measure of the functional redundancy of Hoxa-10 and Hoxa-11 and a deeper understanding of the phenotypes resulting in the single mutants and help elucidate the regulatory interactions between these two genes. (C) 2000 Academic Press.
KW - Functional redundancy
KW - Hox genes
KW - Limbs
KW - Reproductive tract
UR - http://www.scopus.com/inward/record.url?scp=0034663358&partnerID=8YFLogxK
U2 - 10.1006/dbio.2000.9809
DO - 10.1006/dbio.2000.9809
M3 - Article
C2 - 10926774
AN - SCOPUS:0034663358
SN - 0012-1606
VL - 224
SP - 373
EP - 387
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -