a mouse model of the human fragile x syndrome i304n mutation小鼠模型的人类脆性x综合征i304n突变.pdfVIP

A Mouse Model of the Human Fragile X Syndrome I304N Mutation 1 2 3 2 1 1 Julie B. Zang , Elena D. Nosyreva , Corinne M. Spencer , Lenora J. Volk , Kiran Musunuru , Ru Zhong , 1 3 2 3 1 Elizabeth F. Stone , Lisa A. Yuva-Paylor , Kimberly M. Huber , Richard Paylor , Jennifer C. Darnell *, Robert B. Darnell1,4 1 Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, United States of America, 2 Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America, 3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America, 4 Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America Abstract The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 59UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleuc