Replicated anterior zeugopod (raz): a polydactylous mouse mutant with lowered Shh signaling in the limb bud.
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 approximately 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.
Krebs
Ottheinz
O
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilian University, Munich, Germany. krebs@lmb.uni-muenchen.de
Schreiner
Claire M
CM
Scott
William J
WJ
Bell
Sheila M
SM
Robbins
David J
DJ
Goetz
John A
JA
Alt
Heidi
H
Hawes
Norm
N
Wolf
Eckhard
E
Favor
Jack
J
D000818:Animals; D019521:Body Patterning; D007446:Chromosome Inversion; D033481:Chromosomes, Mammalian / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005552:Forelimb / Q000002:abnormalities / Q000033:anatomy & histology* / Q000196:embryology; D005838:Genotype; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D018878:Limb Buds / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D009024:Morphogenesis; D009419:Nerve Tissue Proteins; D000072079:Patched Receptors; D010641:Phenotype; D017689:Polydactyly / Q000235:genetics*; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3