Organization
Brain Research Institute Center for Bioresources Specially Appointed Assistant
Title
Specially Appointed Assistant
External link
HIROKAWA Sachiko
Degree
-
修士 (医科学) ( 2007.3 新潟大学 )
Research History (researchmap)
-
Niigata University Brain Research Institute
2016.11
Research History
-
Niigata University Brain Research Institute Center for Bioresources Specially Appointed Assistant
2016.11
Education
-
Niigata University 医歯学総合研究科 医科学
2005.4 - 2007.3
Research Projects
-
Analysis of TDP-43 functions and modeling for ALS using conditional knockout mice
Grant number：22590925
2010 - 2012
System name：Grants-in-Aid for Scientific Research
Research category：Grant-in-Aid for Scientific Research (C)
Awarding organization：Japan Society for the Promotion of Science
SATO Toshiya, OSAMU Onodera, SACHIKO Hirokawa
Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）
To investigate the physiological functions of TAR DNA-binding protein 43 kDa (TDP-43), we established TDP-43 conditional knockout (cKO) mice and evaluated the validity of disease models for amyotrophic lateral sclerosis (ALS). As a result of the autoregulation, TDP-43 mRNAs were recovered to wild type levels in various tissues of heterozygous TDP-43 KO (Tardbp^+/-) mice. This recovery would prevent from the emergence of abnormal phenotypes. On the other hand, TDP-43 mRNA level in unfertilized oocytes obtained from heterozygous mice was reduced by half. This haploinsufficiency would account for the delay of early embryonic development. Because homozygous (Tardbp^-/-) mice died by early post-implantation stage, we established neuron-specific KO (Tardbp^flox/flox、NSE-Cre^+) mice using NSE39-Cre mice. Neuron-specific KO mice showed sever neurological phenotypes with a median survival of 20 days. Pathologically, chromatolysis and abnormal-shaped mitochondria, characteristic features of ALS, were observed in lumbar motor neurons.