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Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4.

Publication ,  Journal Article
Dunn, NR; Winnier, GE; Hargett, LK; Schrick, JJ; Fogo, AB; Hogan, BL
Published in: Dev Biol
August 15, 1997

Bone morphogenetic protein 4 (Bmp4), a vertebrate homolog of Drosophila decapentaplegic (dpp), encodes a signaling protein with multiple functions during embryogenesis. Most mouse embryos homozygous for the Bmp4(tm1blh) null allele die around the time of gastrulation, with little or no mesoderm. Two independently derived Bmp4(tm1) mutations were backcrossed onto the C57BL/6 genetic background. Several independently expressed, incompletely penetrant abnormalities were observed in heterozygotes, including cystic kidney, craniofacial malformations, microphthalmia, and preaxial polydactyly of the right hindlimb. In addition, heterozygotes were consistently underrepresented at weaning. These results indicate that Bmp4 gene dosage is essential for the normal development of a variety of organs and for neonatal viability. Two mutations that enhance the penetrance and expressivity of the polydactylous phenotype were identified: Gli3(XtJ), a deletion mutation involving a gene encoding a zinc-finger protein related to Drosophila cubitus interruptus, and Alx4(tm1rwm), a targeted null mutation in a gene encoding a paired class homeoprotein related to Drosophila aristaless. All double Bmp4(tm1); Gli3(XtJ) heterozygotes have extensive anterior digit abnormalities of both fore- and hindlimbs, while all double Bmp4(tm1); Alx4(tm1) heterozygotes display ectopic anterior digits only on the hindlimbs. These genetic interactions suggest a model for the multigenic control of anterior digit patterning during vertebrate limb development.

Duke Scholars

Published In

Dev Biol

DOI

ISSN

0012-1606

Publication Date

August 15, 1997

Volume

188

Issue

2

Start / End Page

235 / 247

Location

United States

Related Subject Headings

  • Zinc Finger Protein Gli3
  • Xenopus Proteins
  • Transcription Factors
  • Sex Characteristics
  • Repressor Proteins
  • Polydactyly
  • Phenotype
  • Osteogenesis
  • Nerve Tissue Proteins
  • Mutagenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Dunn, N. R., Winnier, G. E., Hargett, L. K., Schrick, J. J., Fogo, A. B., & Hogan, B. L. (1997). Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol, 188(2), 235–247. https://doi.org/10.1006/dbio.1997.8664
Dunn, N. R., G. E. Winnier, L. K. Hargett, J. J. Schrick, A. B. Fogo, and B. L. Hogan. “Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4.Dev Biol 188, no. 2 (August 15, 1997): 235–47. https://doi.org/10.1006/dbio.1997.8664.
Dunn NR, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BL. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol. 1997 Aug 15;188(2):235–47.
Dunn, N. R., et al. “Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4.Dev Biol, vol. 188, no. 2, Aug. 1997, pp. 235–47. Pubmed, doi:10.1006/dbio.1997.8664.
Dunn NR, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BL. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol. 1997 Aug 15;188(2):235–247.
Journal cover image

Published In

Dev Biol

DOI

ISSN

0012-1606

Publication Date

August 15, 1997

Volume

188

Issue

2

Start / End Page

235 / 247

Location

United States

Related Subject Headings

  • Zinc Finger Protein Gli3
  • Xenopus Proteins
  • Transcription Factors
  • Sex Characteristics
  • Repressor Proteins
  • Polydactyly
  • Phenotype
  • Osteogenesis
  • Nerve Tissue Proteins
  • Mutagenesis