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A study of genetic factors responsible for difference in spontaneous home-cage activity between inbred strains of mouse
https://ir.soken.ac.jp/records/1008
https://ir.soken.ac.jp/records/1008c5c7f902-5296-4684-9183-d29fd49b7aa8
| 名前 / ファイル | ライセンス | アクション |
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要旨・審査要旨 (337.1 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2010-02-22 | |||||
| タイトル | ||||||
| タイトル | A study of genetic factors responsible for difference in spontaneous home-cage activity between inbred strains of mouse | |||||
| タイトル | ||||||
| タイトル | A study of genetic factors responsible for difference in spontaneous home-cage activity between inbred strains of mouse | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| 著者名 |
梅森, 十三
× 梅森, 十三 |
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| フリガナ |
ウメモリ, ジュウゾウ
× ウメモリ, ジュウゾウ |
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| 著者 |
UMEMORI, Juzo
× UMEMORI, Juzo |
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| 学位授与機関 | ||||||
| 学位授与機関名 | 総合研究大学院大学 | |||||
| 学位名 | ||||||
| 学位名 | 博士（理学） | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 総研大甲第866号 | |||||
| 研究科 | ||||||
| 値 | 生命科学研究科 | |||||
| 専攻 | ||||||
| 値 | 18 遺伝学専攻 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2005-03-24 | |||||
| 学位授与年度 | ||||||
| 値 | 2004 | |||||
| 要旨 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | A large part of wild animal life depends on the ability to move from one place to another. This type of behavior is referred to as spontaneous locomotive activity. The activity plays a crucial role in many situations, e.g. avoiding predators, finding food and mating partners, territorial defense, and migration. Hence, the spontaneous locomotive activity is greatly involved in the strategy for survival in the wild life.<br /> In the laboratory, mice move spontaneously in the habituated home-cage according to a light/dark rhythm and most mice are active during the dark period. This kind of activity is described as spontaneous home-cage activity. The activity is quite different quantitatively and qualitatively, depending on the genetic background. Previous genetic studies have clarified that the activity is controlled by multiple genetic factors, quantitative trait loci (QTLs). In a variety of strains, mice of C57BL/6J are relatively hypoactive, in contrast to mice of KJR that are especially hyperactive in the habituated home-cage. The spontaneous home-cage activity is considered as a behavior, which is driven by both the motor function in the central nervous system and the physical ability. Thus, the possible genetic factors influence the spontaneous home-cage activity through regulations of the central nervous system and the physical ability. I worked for elucidating the genetic basis and biological mechanisms that determine the difference in spontaneous home-cage activity between C57BL/6J and KJR.<br /> In order to study the genetic basis responsible for the difference in spontaneous home-cage activity between KJR and C57BL/6J, we tried to detect QTLs associated with the difference. F2 progeny (BKF2) that were made between C57BL/6J and KJR strains were analyzed for their total home-cage activity (THA) in a three-day measurement. Furthermore, I divided THA into two ethological components, active time (AT) and average activity (AA), and used them for the QTL analysis. AT indicates the total time of movement and is considered as the temporal element of THA. AA indicates the average amount of movement during the active time and is considered as the quantitative element of THA. Pearson correlation analyses showed moderate correlation (r = 0.401) between the measurement values of AA and AT. The correlation value suggested that AA and AT were almost independent measurement, and were expected to be associated with independent genetic factors. The QTL analyses identified three significant QTLs involved in the spontaneous home-cage activity. These QTLs were designated as hyperlocomotive activity related QTL1 (Hylaq1), Hylaq2 and Hylaq3. All Hylaq loci were associated with THA. Hylaq1 was located in a middle region of chromosome 2 (chr2), and mainly associated with AT. Hylaq1 contributed to 31 %, 214 % and 5 % of the overall differences in THA, AT and AA, respectively, between KJR and C57BL/6J. Hylaq2 was located on the distal side of Hylaq1 on chr2, and controlled both AT and AA. Hylaq2 contributed to 35 %, 118 % and 21 % of the overall differences in THA, AT and AA, respectively, between KJR and C57BL/6J. Hylaq3 was located near the telomeric region on chr10, and associated with mainly AA. Hylaq3 contributed to 39 %, 81 % and 29 % of the overall differences in THA, AT and AA, respectively, between KJR and C57BL/6J. Thus, the QTL analyses identified three novel QTLs involved in the spontaneous home-cage activity.<br /> In contrast to the home-cage activity, open-field activity is considered to reflect the psychological status of the subject. The open-field test is used to assess the reactivity to a novel environment including animal's exploratory activity and anxiety. Interestingly, C57BL/6J exhibits a hyperactive phenotype in the open-field test for the first one-minute period while KJR is hypoactive. I investigated the open-field activity and compared it with the spontaneous home-cage activity. A Pearson correlation analysis between the open-field activity and the spontaneous home-cage activity showed little association in BKF2. This result suggests that these traits are independent and controlled by independent genetic factors. In fact, a QTL analysis showed a suggestive QTL related to the open-filed activity on chr11 and that no or only few QTLs are common to the spontaneous home-cage activity and the open-field activity. These results suggest that the genetic mechanism involved in the spontaneous home-cage activity is different from the mechanism associated with the open-field activity. <br /> It has been reported that the dopamine (DA) system in basal ganglia of the brain is associated with movement and spontaneous locomotive activity. To search for candidate genes in the above QTL regions, and to understand the biological mechanisms that are associated with the spontaneous home-cage activity, phenotypic analyses on the DA system have been conducted with pharmacological and biochemical methods. As a first step, the effects of dopamine-related drugs on home-cage activity were investigated. A D1-like receptor selective agonist (SKF38393), a D2-like selective agonist (quinpirole), and a DA transporter (DAT) blocker (methylphenidate-hydrochloride, MPH) were administered to mice, and the behavioral alternations were observed in C57BL/6J and KJR. As a second step, the expression levels of tyrosine hydroxylase (Th) and DAT, which are involved in the synthesis of DA and up-take of the released DA in the synapses, respectively, were analyzed. As a third step, I tried to determine the basal level of extracellular (extraneuronal) DA released from the terminals of dopaminergic neurons in the striatal synapses by a microdialysis method. Finally, the released DA levels were measured by the microdialysis method following acute administration of MPH, which prevents DA re-uptake and induces extracellular accumulation of DA proportional to the amount of release from the nerve terminals. The expression analysis and microdialysis analysis suggested that there was no difference in DA synthesis, release or uptake in the presynapse of the dopaminergic neurons between KJR and C57BL/6J. The results of the pharmacological analyses indicate that the differences in the spontaneous home-cage activity between these strains might be due to the pharmacological differences in the downstream of the DA system following activation of the DA receptors. In particular, function of D1 DA pathway that regulates the spontaneous activity negatively is possibly reduced in KJR but not in C57BL/6J.<br /> In the Hylaq regions, there are many genes expressed in the central nervous system. However, none of them seems directly involved in the DA pathway. Further functional analysis of the genes in the region should reveal the genetic basis of the regulation of spontaneous locomotive activity. | |||||
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| 値 | 有 | |||||
