2004 Fiscal Year Final Research Report Summary
Memory and learning disorder analysis using mutation mouse for mental retadation related gene ATRX and elucidation of the genetic control abnormality.
| Project/Area Number |
15500210
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KITAJIMA Isao Toyama Med Pharmaceut Univ., Lab Med., Professor, 医学部, 教授 (50214797)
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| Co-Investigator(Kenkyū-buntansha) |
NIHIJO Hisao Toyama Med Pharmaceut Univ., Lab Med., Professor, 大学院・医学系研究科, 教授 (00189284)
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| Project Period (FY) |
2003 – 2004
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| Keywords | ATRX syndrome / Knock out mouse / learning, behavior disorder / behavior analysis / cerebral cortex / hippocampus / cerebellum / Morris water maze |
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| Research Abstract |
The causative gene of the ATRX syndrome, which maps on chromosome X and shows such phenotypes as mental retardation and α thalassemia, is clarified. It has been reported that intelligence is lowered when exon 2 is mutated. Then, in cooperation with Dr.En Li and Dr.H.Beppu (Harvard University, USA), we performed back-crossing in the C57BL6 mouse system from the 129 mouse system to six generations (N6) in order to produce the ATRX mutant mouse for behavioral analysis. Using the C75BL6, N6 generation mouse, the following results were obtained over the two-year research period from 2003 to 2004. (1) The mutant mice have kock in highly Lac Z gene at the mutation site. The Lac Z gene was well observed in the hippocampus, cerebral cortex and cerebellum by X-gal staining. (2) Immunostaining was carried out with an antibody that recognized the C-terminus of ATRX. As a result, in comparison with the wild type, the low expression of the ATRX protein in the cerebral cortex, cerebellum, and hippoca
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mpus was recognized in the ATRX mutant mouse. (3) Using the antibody that recognized the C-terminus of ATRX, the mutant mouse showed decreased protein expression of approximately 50% in brain tissues by Western blot, in comparison with the wild type. (4) It is well known that the hippocampus controls memory and learning. Therefore, in order to analyze its function, we examined spatial memory learning with the Morris water maze test, and found that memory and learning capability of the mutant mouse were inferior to those of the wild type. This finding was confirmed in the diet remuneration test under the environment which removed aquaphobia. We also performed the open field test and the home cage activity test in order to examine other behavioral disorders of the mutant mouse. From these tests, we noted hyperactivity in the mutant mouse. Although it was affected by bright light in the wild type mouse, the sojourn time in the light-dark environment was reversed in the mutant mouse. The behavioral analysis revealed that the ATRX mutant mouse presented with low learning capability, photophobia sensitivity and hyperactivity. Less
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Research Products
(16 results)
