reversal of fragile x phenotypes by manipulation of aβppaβ levels in fmr1ko mice的脆性x表型逆转操纵aβppaβ水平fmr1ko老鼠.pdfVIP

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reversal of fragile x phenotypes by manipulation of aβppaβ levels in fmr1ko mice的脆性x表型逆转操纵aβppaβ水平fmr1ko老鼠.pdf

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reversal of fragile x phenotypes by manipulation of aβppaβ levels in fmr1ko mice的脆性x表型逆转操纵aβppaβ水平fmr1ko老鼠

Reversal of Fragile X Phenotypes by Manipulation of AbPP/Ab Levels in Fmr1KO Mice 1 1 2 1 4 Cara J. Westmark *, Pamela R. Westmark , Kenneth J. O’Riordan , Brian C. Ray , Crystal M. Hervey , M. 3 1 1 1 7 Shahriar Salamat , Sara H. Abozeid , Kelsey M. Stein , Levi A. Stodola , Michael Tranfaglia , Corinna Burger2, Elizabeth M. Berry-Kravis4,5,6, James S. Malter1,3¤ 1 Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, Wisconsin, United States of America, 2 Department of Neurology, University of Wisconsin, Madison, Wisconsin, United States of America, 3 Department of Pathology Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, United States of America, 4 Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, United States of America, 5 Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, United States of America, 6 Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, United States of America, 7 FRAXA Research Foundation, Newburyport, Massachusetts, United States of America Abstract Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid b-protein precursor (AbPP) mRNA. Cleavage of AbPP can produce b-amyloid (Ab), a 39–43 amino acid peptide mis-expressed in Alzheimer’s disease (AD) and Down syndrome (DS). Ab is over-expres