國立虎尾科技大學 |

Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development./
Author:	Volpatti, Jonathan.
Description:	1 online resource (83 pages)
Notes:	Source: Masters Abstracts International, Volume: 57-01.
Subject:	Molecular biology. -
Online resource:	click for full text (PQDT)
ISBN:	9780355452945

Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development.
Volpatti, Jonathan.

Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development. - 1 online resource (83 pages)

Source: Masters Abstracts International, Volume: 57-01.

Thesis (M.Sc.)--University of Toronto (Canada), 2017.

Includes bibliographical references

X-linked centronuclear myopathy (XLCNM) is a congenital skeletal muscle disorder caused by mutations in MTM1. Despite being associated with a high rate of neonatal mortality there are currently no effective therapies for this disorder. MTM1 is a phosphoinositide 3-phosphatase that antagonizes class II and III phosphatidylinositol 3-kinases (PI3K). Loss of Pik3c2b, a class II PI3K, rescues lethality in Mtm1 knockout mice. Importantly, Pik3c2b knockout mice are viable and have no apparent phenotype. Therefore, pharmacological inhibitors of PIK3C2B have the potential to be highly effective in the treatment of XLCNM. I have characterized an mtm1 mutant using the zebrafish, Danio rerio, and found that PIK3C2B inhibition improves the mtm1 mutant phenotype. In parallel, a phenotypic drug screen identified valproic acid as a suppressor of an mtm1 mutant phenotype. The work presented herein demonstrates that PIK3C2B inhibitors and drugs like valproic acid may represent putative therapeutics for translation into MTM1 patients.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9780355452945Subjects--Topical Terms:

583443
Molecular biology.
Index Terms--Genre/Form:

554714
Electronic books.

Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development.
LDR:02214ntm a2200325K 4500 001 913359
005 20180618102637.5
006 m o u
007 cr mn||||a|a||
008 190606s2017 xx obm 000 0 eng d
020 $a 9780355452945
035 $a (MiAaPQ)AAI10636479
035 $a (MiAaPQ)toronto:16563
035 $a AAI10636479
040 $a MiAaPQ $b eng $c MiAaPQ
100 1 $a Volpatti, Jonathan. $3 1186168
245 1 0 $a Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development.
264 0 $c 2017
300 $a 1 online resource (83 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Masters Abstracts International, Volume: 57-01.
500 $a Adviser: James J. Dowling.
502 $a Thesis (M.Sc.)--University of Toronto (Canada), 2017.
504 $a Includes bibliographical references
520 $a X-linked centronuclear myopathy (XLCNM) is a congenital skeletal muscle disorder caused by mutations in MTM1. Despite being associated with a high rate of neonatal mortality there are currently no effective therapies for this disorder. MTM1 is a phosphoinositide 3-phosphatase that antagonizes class II and III phosphatidylinositol 3-kinases (PI3K). Loss of Pik3c2b, a class II PI3K, rescues lethality in Mtm1 knockout mice. Importantly, Pik3c2b knockout mice are viable and have no apparent phenotype. Therefore, pharmacological inhibitors of PIK3C2B have the potential to be highly effective in the treatment of XLCNM. I have characterized an mtm1 mutant using the zebrafish, Danio rerio, and found that PIK3C2B inhibition improves the mtm1 mutant phenotype. In parallel, a phenotypic drug screen identified valproic acid as a suppressor of an mtm1 mutant phenotype. The work presented herein demonstrates that PIK3C2B inhibitors and drugs like valproic acid may represent putative therapeutics for translation into MTM1 patients.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Molecular biology. $3 583443
650 4 $a Genetics. $3 578972
655 7 $a Electronic books. $2 local $3 554714
690 $a 0307
690 $a 0369
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of Toronto (Canada). $b Molecular and Medical Genetics. $3 1186169
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10636479 $z click for full text (PQDT)