2007 Fiscal Year Final Research Report Summary
ANALYSIS OF FUNCTION OF THE DISEASE-RESPONSIBLE GENIE Nnal FOR A MUTANT MOUSE EXHIBITING CEREBELLAR ATAXIA AND MALE STERILITY
| Project/Area Number |
17590347
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Shimane University |
|---|
Principal Investigator |
HARADA Takayuki Shimane University, SCHOOL OF MEDICINE, DEPARTMENT OF PATHOLOGY, PROFESSOR (90112135)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHIRA Akihiro SHIMANE UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF OPHTHALMOLOGY, PROFESSOR (00169054)
NAKANO Akinobu SHIMANE UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF PATHOLOGY, PROFESSOR (70263514)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Keywords | CEREBELLAR ATAXIA / PURKINJYE CELL / APOPTOSIS / CASPASE / NEURAL CELL DEATH / AMS MOUSE / MUTANT / Nnal GENE |
|---|
| Research Abstract |
The Ataxia and Male Sterility (AMS) mouse is a mutant that exhibits ataxia due to a near-complete loss of the cerebellar Purkinje cells and male sterility because of severe oligospermia due to the degeneration and death of differentiating germ cells in the serniniferous tubules. The disease-responsible ams gene was shown to be allelic to Nnal, of which the biochemical function remains to be elucidated. A RT-PCR analysis to sequentially cover the whole transcript of the Nnal gene revealed that no obvious differences in either the size or quantity of the mRNA. By sequencing the cDNA base pairs a point mutation of .G to C was detected at 2423bp in exon 17. This missense mutation caused 808th arginie → proline and it appeared to affect the protein structure and stability, because the transfection of the cDNA construct of the wild-type, but not of the mutant, led to the translation and stable expression of the protein.
To investigate how ams mutation affects the cellular processes, we devote
… More
d our efforts to the morphological analysis of the mode of cell death. The causes of the acute pathological atrophy of the AMS cerebellum were not only the primary near complete loss of the Purkinje cells but also the secondary damage to other cells. Dying Purkinje cells lacked the characteristics of classical apoptosis, but in the granular layer typical apoptotic bodies were recognized by electron microscopy, and a substantial number of TUNEL-positive cells and activated caspase-3-positive cells were observed. Thus death of Purkinje cells appeared to be autonomous, whereas granule cell death was considered to be target-related apoptosis. Another study on:the photic injury of the photoreceptor cell of the AMS retina revealed that the cells had lost the ability to resist such injurious factors while, in addition, the process of apoptotic cell death was also different from that of classical apoptosis. Since the ams mutation affects the dying process of many cell types in different manners, Nnal is likely to act as an important regulator of the life of cells. Less
|
Research Products
(28 results)
-
-
-
-
[Journal Article] emsmutation of the disease-responsibleAheigene of the Ataxia and Male Sterility (AMS) mouse and its different types of cell death(The selected paper of the meeting)2006
Author(s)
Li, Zhou, Jie, Zhang, Asuka, Araki, Akinobu, Nakano, Takayuki, Harada, Masao, Ono, Masato, Nose
-
Journal Title
Proceedings of the Japanese Society of Animal Models for Human Diseases 22
Pages: 19-25
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Immortalized Human Microglial cell Line2005
Author(s)
Atushi Nagai, Seiji Mishima, Yuri Ishida, Hiroto Ishikura, Takayuki Harada, Syotai Kobayashi, Seune U. Kim
-
Journal Title
Phenotypic Expresson Journal of Neuroscience Research 81
Pages: 001-007
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
-
[Journal Article] Kim : Immortalized Human Microglial cell Line. Phenotypic Expresson2005
Author(s)
Atushi, Nagai, Seiji, Mishima, Yuri, Ishida, Hiroto, Ishikura, Takayuki, Harada, Syotai, Kobayashi, Seung, U
-
Journal Title
Journal of Neuroscience Research 81
Pages: 001-007
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
[Presentation] The ams mutation of the Arnal gene of the Ataxia and Male Sterility mouse is a point mutation that affects expression of the protein but not transcription of the mRNA2006
Author(s)
Takayuki, Harada, Asuka, Araki, Akinobu, Nakano, Tie, Zhang, Atsushi, Nagai, andMasao, Ono
Organizer
Neuroscience 2006, 36th annual meeting of the Society for Neuroscience
Place of Presentation
Atlanta
Year and Date
20061000
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Presentation] Ataxia and Male Sterility (AMS) Mutant Mouse : Functional loss of a single gene (final) leads to various histo- and cyto-pathological changes2006
Author(s)
Takayuki, Harada, Asuka, Araki, Li, Zhou, Jie, Zhang, Akinobu, Nakano, Masao, Ono, Masato Nose
Organizer
3rd Pathology Conference of the Japanese Society of Pathology
Place of Presentation
Tokyo
Year and Date
20060800
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Effeet of the ems mutation in the Ataxia and Male Sterility (AMS) mouse on photic injury to photoreceptor cells2006
Author(s)
Asuka, Araki, Akinobu, Nakano, Li, Zhou, Riruke, Maruyama, Akihiro, Ohira, Takaybki, Harada
Organizer
The Seventh Joint Meeting of the Japan Society of Histochemistry and Cytochemistry and the US Histochemical Society. Waikoloa
Place of Presentation
Hawaii
Year and Date
20060800
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Presentation] Neural and Male Germ Cell Mutant AMS Mouae : 13. genetic analysisof the disease-responsible ams mutation2006
Author(s)
Takayuki, Harada, Jie, Zhang, Asuka, Araki, Akinobn, Nakano, Li, Zhou, Masao, One, Masato, Nose
Organizer
95th Annual Meeting of the Japanese Society of Pathology
Place of Presentation
Tokyo
Year and Date
20060400
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Presentation] Neural and Male ; Genstell Mutant ARS Mouse : 12. ems mutation of the disease-responsible gene and different types of cell death2005
Author(s)
Li, Zhoti, Jie, Zhiag, AsUka, Araki, Akinobu, Nakano, Masao, Ono, Masato Nnae, TakaYuki, Harada
Organizer
22nd Annual Meeting of the Japanese Society of Animal Models for Human Diseases
Place of Presentation
Ikaho
Year and Date
20051100
Description
「研究成果報告書概要(欧文)」より
-
-
[Presentation] Neural and Male GermCell Mutant : AMS Mouse : 41. Acceleration of the PhOtoieceptot Cell Death by Photic Injury in AMS Retina2005
Author(s)
Li, Zhbu, Asuka, Araki, AkinobuNakano, Yu, Ryu, Akihiro, Ohira, lakayuki, Harada
Organizer
46th AnnOrMeatina of the Japanese Society forthStoebeinittrYand-Cytochemistry
Place of Presentation
Kyoto
Year and Date
20051000
Description
「研究成果報告書概要(欧文)」より
-
-
