title: Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA.
abstract: Construction of animal models of human inherited diseases is particularly important for testing gene therapy approaches. Towards this end, we constructed a mouse model for Charcot-Marie-Tooth disease type 1A by pronuclear injection of a YAC containing the human PMP22 gene. In one transgenic line, the YAC DNA is integrated in about eight copies and the PMP22 gene is strongly expressed to give a peripheral neuropathy closely resembling the human pathology. The disorder is dominant, causes progressive weakness of the hind legs, and there is severe demyelination in the peripheral nervous system including the presence of onion bulb formations. This approach will be valuable for pathologies produced by over-expression of a gene including trisomy and amplification in cancer. Such models will be particularly useful for testing gene therapy approaches if the transgene is human.
authors: Imperial College School of Medicine at St Mary's, London, UK.
authors: C
authors: C
authors: Huxley
authors: E
authors: E
authors: Passage
authors: A
authors: A
authors: Manson
authors: G
authors: G
authors: Putzu
authors: D
authors: D
authors: Figarella-Branger
authors: J F
authors: JF
authors: Pellissier
authors: M
authors: M
authors: Fontés
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012584:Sciatic Nerve / Q000737:chemistry / Q000648:ultrastructure; D014018:Tissue Distribution
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; C489545:Pmp22 protein, mouse; D012333:RNA, Messenger