Replicated anterior zeugopod (raz): A polydactylous mouse mutant with lowered Shh signaling in the limb bud

Ottheinz Krebs, Claire M. Schreiner, William J. Scott, Sheila M. Bell, David J Robbins, John A. Goetz, Heidi Alt, Norm Hawes, Eckhard Wolf, Jack Favor

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A unique limb phenotype is described in a radiation-induced mutant mouse resulting from an inversion of a proximal segment of chromosome 5. The limb phenotype in the homozygous mutant presents with two anterior skeletal elements in the zeugopod but no posterior bone, hence the name replicated anterior zeugopod, raz. The zeugopod phenotype is accompanied by symmetrical central polydactyly of hand and foot. The chromosomal inversion includes the Shh gene and the regulatory locus, located ∼1 Mb away, within the Lmbr1 gene. In homozygous mutants, the expression of Shh mRNA and Shh protein is severely downregulated to about 20% of wild-type limb buds, but Shh expression appears normal throughout the remainder of the embryo. Correspondingly, Gli3 expression is upregulated and posteriorly expanded in the raz/raz limb bud. We propose that the double anterior zeugopod and symmetrical central polydactyly are due to an increased and uniform concentration of the Gli3 repressor form because of lowered Shh signaling.

Original languageEnglish
Pages (from-to)6037-6047
Number of pages11
JournalDevelopment
Volume130
Issue number24
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Limb Buds
Polydactyly
Phenotype
Extremities
Chromosomes, Human, Pair 5
Regulator Genes
Names
Foot
Down-Regulation
Embryonic Structures
Hand
Radiation
Bone and Bones
Messenger RNA
Genes
Proteins

Keywords

  • Central polydactyly
  • Gli3
  • Mouse
  • Radial and tibial dimelia
  • Sonic hedgehog

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Krebs, O., Schreiner, C. M., Scott, W. J., Bell, S. M., Robbins, D. J., Goetz, J. A., ... Favor, J. (2003). Replicated anterior zeugopod (raz): A polydactylous mouse mutant with lowered Shh signaling in the limb bud. Development, 130(24), 6037-6047. https://doi.org/10.1242/dev.00861

Replicated anterior zeugopod (raz) : A polydactylous mouse mutant with lowered Shh signaling in the limb bud. / Krebs, Ottheinz; Schreiner, Claire M.; Scott, William J.; Bell, Sheila M.; Robbins, David J; Goetz, John A.; Alt, Heidi; Hawes, Norm; Wolf, Eckhard; Favor, Jack.

In: Development, Vol. 130, No. 24, 01.12.2003, p. 6037-6047.

Research output: Contribution to journalArticle

Krebs, O, Schreiner, CM, Scott, WJ, Bell, SM, Robbins, DJ, Goetz, JA, Alt, H, Hawes, N, Wolf, E & Favor, J 2003, 'Replicated anterior zeugopod (raz): A polydactylous mouse mutant with lowered Shh signaling in the limb bud', Development, vol. 130, no. 24, pp. 6037-6047. https://doi.org/10.1242/dev.00861
Krebs, Ottheinz ; Schreiner, Claire M. ; Scott, William J. ; Bell, Sheila M. ; Robbins, David J ; Goetz, John A. ; Alt, Heidi ; Hawes, Norm ; Wolf, Eckhard ; Favor, Jack. / Replicated anterior zeugopod (raz) : A polydactylous mouse mutant with lowered Shh signaling in the limb bud. In: Development. 2003 ; Vol. 130, No. 24. pp. 6037-6047.
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