Deletion of a conserved noncoding sequence in Plzf intron leads to Plzf down-regulation in limb bud and polydactyly in the rat
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19191224
DOI
10.1002/dvdy.21859
Knihovny.cz E-resources
- MeSH
- Gene Deletion MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- Down-Regulation genetics MeSH
- Embryo, Mammalian embryology metabolism MeSH
- Introns genetics MeSH
- Limb Buds abnormalities metabolism MeSH
- Conserved Sequence MeSH
- Rats MeSH
- RNA, Messenger genetics MeSH
- RNA, Untranslated genetics MeSH
- Polydactyly genetics metabolism MeSH
- Promyelocytic Leukemia Zinc Finger Protein MeSH
- Body Patterning MeSH
- Base Sequence MeSH
- Gene Expression Regulation, Developmental MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA-Binding Proteins MeSH
- RNA, Messenger MeSH
- RNA, Untranslated MeSH
- Promyelocytic Leukemia Zinc Finger Protein MeSH
- ZBTB16 protein, rat MeSH Browser
Lx mutation in SHR.Lx rat manifests in homozygotes as hindlimb preaxial polydactyly. It was previously mapped to a chromosome 8 segment containing the Plzf gene. Plzf (promyelocytic leukemia zinc finger protein) influences limb development as a direct repressor of posterior HoxD genes. However, the Plzf coding sequence is intact in the Lx mutants. Using linkage mapping in F2 hybrids, we downsized the segment containing Lx to 155 kb and sequenced conserved noncoding elements (CNEs) inside. A 2,964-bp deletion in Plzf intron 2, never detected in control animals, is the only candidate for Lx. The deletion removes the most deeply conserved CNE in the 155-kb segment, suggesting a regulatory influence on Plzf expression. Correspondingly, using in situ hybridization and quantitative real-time polymerase chain reaction, we found a decrease of Plzf expression in Lx/Lx limb buds with concomitant anterior expansion of expression domains of its targets, Hoxd10-13 genes, in the absence of ectopic Sonic hedgehog expression. Upstream regulation of Plzf in limb buds is currently unknown. We present here the first candidate Plzf cis-regulatory sequence.
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