Transgenic Mouse Models of CAG Trinucleotide Repeat Neurologic Diseases

摘要: During the past few years a new class of mutation has burst upon human genetics scene, resulting in rethinking some basic principles Mendelian genetics. This form mutation, termed unstable trinucleotide repeats, is dynamic that produced by heritable DNA. For reasons not understood, these mutations seem to effect predominately genes whose function critical for neuromuscular tissue. To date 12 diseases have been characterized as caused expansion an repeat.Among are fragile XA (Kremer et al., 1991; Verkerk Yu 1991) and XE (Knight 1993) syndromes, myotonic dystrophy(Brook 1992; Mahadevan 1992), spinal bulbar muscular atrophy (SBMA) (LaSpada 1991), Huntington disease (HD) (Huntington’s Disease Research Collaborative Group, 1993), Friedreich’s ataxia (Campuzano 1996), dentatrubral—pallidoluysian (DRPLA) (Koide et., 1994; Nagafuchi 1994)/Haw River syndrome (Burke 1994), spinocerebellar ataxias SCA1 (Orr SCA2 (Imbert 1996; Pulst Sanpei SCA3/Machado-Joseph (MJD) (Kawaguchi SCA6 (Zhuchenko 1997), SCA7 (Stevanin 1996).