title: Pallister-Hall syndrome phenotype in mice mutant for Gli3.
abstract: Mutations in the GLI3 gene have been identified in several human malformation syndromes. One of these autosomal dominant developmental disorders is Pallister-Hall syndrome (PHS; MIM146510), which is associated with central polydactyly and other malformations. Interestingly, the mutations in the GLI3 transcription factor gene identified in patients with PHS are restricted to the region 3' of the zinc finger-encoding domain, leaving this DNA-binding domain intact. We have investigated the consequences of this mutation on the development of multiple organ systems by introducing a targeted mutation in mice. We found that mice homozygous for the mutation showed a central polydactyly, thus modeling one of the major abnormalities of the human syndrome. Moreover, Gli3-mutant mice displayed a wide range of developmental abnormalities encompassing almost all of the common PHS features, including imperforate anus, gastrointestinal, epiglottis and larynx defects, abnormal kidney development, and absence of adrenal glands. Thus, our Gli3-mutant mice provide an excellent model for studies of both the pathogenesis of PHS and Gli3 functions in the development of the affected organ systems.
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Böse
authors.forename: Lars
authors.initials: L
authors.lastname: Grotewold
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rüther
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001006:Anus, Imperforate / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D006222:Hamartoma / Q000235:genetics*; D007027:Hypothalamic Diseases / Q000235:genetics* / Q000473:pathology; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins; D017689:Polydactyly / Q000235:genetics* / Q000473:pathology; D012097:Repressor Proteins; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3
chemical_list: D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3