╨╧рб▒с>■  %'■   $                                                                                                                                                                                                                                                                                                                                                                                                                                                ье┴q`Ё┐ bjbjqPqP .::       д°°°°°°° ┤┤┤┤ └ , ·ррррррррл н н н н н н $& hОю╤ °CррCC╤ °°ррц ╗ ╗ ╗ CB°р°рл ╗ Cл ╗ ╗ °°╗ р╘ pд╨I:Г╞┤Е ╗ П № 0, ╗ |Ы |╗ |°╗ ╘р0"╗ 2Nїррр╤ ╤ е ррр, CCCC   DPd   P   °°°°°°      Measuring calpain 3 proteolytic activity using an in vitro substrate Astrid Milic, Nathalie Daniele, Marc Bartoli, Hans Lochmuller, Marina Mora, Giacomo Comi, Maurizio Moggio, Fanny Noulet, Jerome Poupiot, Isabelle Richard Gщnщthon, Centre National de la Recherche Scientifique UMR 8115, Evry, France Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive muscular disorder caused by mutations in the gene coding for calpain 3, a calcium-dependent protease. In order to improve LGMD2A diagnosis, we have developed an in vitro assay that can detect the proteolytic activity of calpain 3 in a muscle sample. This assay is based on the use of an inactive calpain 3 as a substrate for active calpain 3 molecules. A total of 79 human biopsies consisting of 42 confirmed LGMD2A and 37 other samples (normals, others myopathies and undiagnosed muscles) have been analyzed. Proteolytic activity was either reduced or absent in 68% of LGMD2A biopsies. In the remaining 32%, normal proteolytic activity was found despite the presence of calpain 3 mutation(s), suggesting that other calpain 3 properties, possibly in vivo recognition of physiological substrates or correct calpain 3 localisation in muscle fiber, might be impaired to give rise to the LGMD2A phenotype. 4<Gфх6 ц ! ) k s     ∙ч╥ч─╣∙жТ|Т|ТkWA╣2╣h2Z▄h2Z▄OJQJmH sH *h2Z▄h2Z▄5БCJOJQJ\БaJmH sH 'h2Z▄h2Z▄CJOJQJ\БaJmH sH !h2Z▄CJOJQJ\БaJmH sH *h2Z▄h2Z▄6БCJOJQJ\БaJmH sH 'h2Z▄h2Z▄CJOJQJ\БaJmH sH $h2Z▄h2Z▄CJOJQJaJmH sH h2Z▄h2Z▄mH sH h2Z▄h2Z▄5Б\БmH sH (h2Z▄h2Z▄5Б6БCJ\Б]БaJmH sH "h2Z▄h2Z▄5БCJ\БaJmH sH  h2Z▄h2Z▄GHIуфх3 4 5 6 ¤¤╙╙╙╙╙й╙ВВВ&$d%d&d'dN╞ O╞ P╞ Q╞ gd2Z▄)$$d%d&d'dN╞ O╞ P╞ Q╞ a$gd2Z▄)$$d%d&d'dN╞ O╞ P╞ Q╞ a$gd2Z▄  ■6   ╙╬╬╞──$a$gd2Z▄gd2Z▄+dрдЁ$d%d&d'dN╞ O╞ P╞ Q╞ gd2Z▄,1Рh░В. ░╞A!░Й"░Й#РЙ$РЙ%░░─░─ Р─ЖЬ@@ё @ NormalCJ_HaJmH sH tH :AЄ б: Police par dщfautViє │V Tableau NormalЎ4╓ l4╓aЎ 2kЇ ┴2 Aucune listeNB@ЄN 2Z▄Corps de texte$a$CJOJQJaJ     GHIуфх3456   Ш0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ0ААШ@0ААШ0ААШ0АААШ0ААШ0ААI6█╩00А█╩00А 00N 6     h╨<╣┼i╨lН╨j╨№j╬┼d╔h>*Аurn:schemas-microsoft-com:office:smarttags АPersonNameАC*Аurn:schemas-microsoft-com:office:smarttagsАmetricconverterА г█А3 inА3, aАla Recherche Scientifique АProductID !PUnu|ЖХЬЭбм▓║└╔╨хэlu╜─DO\cип╠╙6=FP~Йшє&LSжн╟╠√╦√/х.гu╝QYZ^ !б,ё-▌G6ЭYB█!CЖKFЕI╖YK╨M9FT8q№sСZw>{ tДlpЛКП/$СOlФc?Ш░7аБиI7йЛлЁ ╖F╛╔°L╔]N╩┬~╠@Y╤ж2█Qo█2Z▄╛CсuтСDхV2ъ9wъЩJ∙╜?№=¤I e!0e!0 @А<Б> @@  Unknown            GРюЗz А Times New Roman5РАSymbol3&Рю Зz А ArialCFРюЗЯComic Sans MS"1ИЁ─йЙье&Йье&└L └L !ЁЙЙ┤┤ББ4   2ГqЁHP Ё ?ф                     2Z▄2  DMeasuring calpain 3 proteolytic activity using an in vitro substrateAdministrateurNina Canki-Klain■ рЕЯЄ∙OhлС+'│┘0─РШшЇ $8 T` А М Шдм┤╝тHMeasuring calpain 3 proteolytic activity using an in vitro substrateAdministrateur Normal.dotNina Canki-Klain2Microsoft Office Word@F├#@602:Г╞@602:Г╞└L■ ╒═╒Ь.УЧ+,∙о04 hpДМФЬ дм┤╝ ─ т Genethon  ц EMeasuring calpain 3 proteolytic activity using an in vitro substrate Titre ■    ■   ■    !"#■   ¤   &■   ■   ■                                                                                                                                                                                                                                                                                                                                                               Root Entry         └Fp┘▄I:Г╞(А1Table         WordDocument        .SummaryInformation(    DocumentSummaryInformation8            CompObj            q                        ■                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           ■       └FDocument Microsoft Office Word MSWordDocWord.Document.8Ї9▓q