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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃憲松 | zh_TW |
| dc.contributor.advisor | Hsien-Sung Huang | en |
| dc.contributor.author | 許琪琳 | zh_TW |
| dc.contributor.author | Chi-Lin Hsu | en |
| dc.date.accessioned | 2021-07-11T15:34:55Z | - |
| dc.date.available | 2024-02-28 | - |
| dc.date.copyright | 2018-10-09 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Wutz, A., Chapter 11 - RNA-Mediated Silencing Mechanisms in Mammalian Cells, in Progress in Molecular Biology and Translational Science, X. Cheng and R.M. Blumenthal, Editors. 2011, Academic Press. p. 351-376.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78993 | - |
| dc.description.abstract | 基因印痕是一種在表觀遺傳學中的特殊現象：透過表觀遺傳的調控，使特定一群基因並非表現父母雙方的基因，而是僅表現父方或母方的基因，這些特別的基因稱為印記基因，過去在胎盤與胎兒中被大量發現，而他們的功能多與發育相關。此外，這些印記基因未必在其他組織中也有基因印痕現象，但近年來發現有部分印記基因在大腦也有基因印痕現象。Retrotransposon-Like 1(Rtl1)是一個與胎盤、胎兒發育息息相關的基因，位於小鼠的第12套染色體上、人類的第14套染色體上，它在胎盤的微血管內皮細胞中大量表現。在Rtl1缺失小鼠模型中，發現父方的Rtl1缺失會造成胎鼠與胎盤的異常，小鼠在發育後期或出生一兩天內死亡，僅有少部分能夠存活，且這些存活下來的胎鼠有發育遲緩的現象，而母方的Rtl1缺失小鼠被發現胎盤會稍大，但出生率與體型並未受到影響。在人類單親源二倍體的患者中，當兩個第14套染色體均來自父方時，這些患者為鏡-緒方症候群(Kagami-Ogata syndrome)，反之則稱為Temple syndrome。這些Temple syndrome的患者的病徵包含肌肉無力、身高矮小與低出生體重、性早熟，我進而推測Rtl1的功能可能是與掌管性腺發育的神經內分泌系統：下視丘－腦垂腺－性腺軸之調節有關。藉由CRISPR-Cas9的系統製造出的Rtl1剃除小鼠中我發現其性腺激素釋放素與濾泡刺激素均有顯著的上升，而性腺激素釋放素的受器表現量則有顯著的下降，但詳細的分子機制仍須進一步探討。在這個研究中藉由測量基因與激素的表現量可以知道，Rtl1的缺失會影響下視丘－腦垂腺－性腺軸的表現，進而影響小鼠的性發育。 | zh_TW |
| dc.description.abstract | Imprinted genes are a subset of genes which show parent-of-origin-specific expression through epigenetic modulation. These genes are known to function for placenta and fetal development and many of them are placenta-specifically imprinted and biallelic expressed in other tissues. Some of the imprinted genes are found imprinted in the brain, and the function is still not fully understood. Retrotransposon-Like 1 (Rtl1), which is imprinted in the brain, has been known for its critical function in endothelial cells of the fetal capillaries of the placenta. Previous studies have shown that Rtl1 paternal knockout mice tend to have phenotypes such as prenatal and neonatal death and growth retardation. Rtl1 maternal knockout mice showed no lethality in pre- or postnatal but are associated with placentomegaly. Human patients with Uniparental disomy (UPD) of chromosome 14 are associated with Temple syndrome (maternal UPD) and Kagami-Ogata syndrome (paternal UPD). It is known that deletion of Rtl1 may relate to less birth weight and height, hypotonia, and premature puberty. I then hypothesized that Rtl1 is involved in regulating sexual maturation. In this thesis, I am interested in studying whether RTL1 plays a role in the hypothalamus-pituitary gland-gonadal (HPG) axis, which is involved in the regulation of puberty. I investigated the potential role with the Rtl1 knockout mice generated by CRISPR/Cas9 system. The experimental outcomes showed that Rtl1 paternal knockout mice have higher Gonadotropin-releasing hormone (GnRH) and Follicle-stimulating hormone (FSH) and lower Gonadotropin-releasing hormone receptor (GnRHR) expression. However, whether these observations are associated with precocious puberty still needs further investigation. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:34:55Z (GMT). No. of bitstreams: 1 ntu-107-R05454011-1.pdf: 4030323 bytes, checksum: 37f02a0e19fd72996f28c96c0aebdc46 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | CONTENTS
誌謝 …………………………………………………………………………………II 中文摘要 …………………………………………………………………………III Abstract………………………………………………………………………………VI 目錄 …………………………………………………………………………………V Chapter 1. Introduction 1 1.1 Brief introduction to genomic imprinting 1 1.2 Dlk1-Dio3 locus 2 1.3 Uniparental disomy (14) 4 1.4 Retrotransposon-Like 1 (Rtl1) and Rtl1 antisense 5 1.5 Hypothalamus-Pituitary-Adrenal-axis (HPA-axis) 6 1.6 Hypothalamus-Pituitary-Gonadal-axis (HPG-axis) 8 1.7 Previous study and limits 9 1.8 Aim of the study 10 Chapter 2. Material and Methods 11 2.1 Animals 11 2.2 Genotyping 11 2.3 Sanger sequencing 12 2.4 Tissue RNA extraction 12 2.5 Reverse transcription 13 2.6 Polymerase Chain Reaction(PCR) 13 2.7 Real-Time quantitative PCR (RT-qPCR) 14 2.8 TA cloning 14 2.9 Histology 15 2.10 Western Blotting 15 2.11 Enzyme-Linked Immunosorbent Assay (ELISA) 16 2.12 Statistical Analysis 16 Chapter 3. Results 17 3.1 RTL1 express in the brain, adrenal gland, and placenta in the mouse 17 3.2 Investigating the mechanisms of differentially expression level of Rtl1 in different brain regions 17 3.3 Rtl1 expresses different isoforms but all paternally expressed in the pituitary gland and adrenal gland of HPA axis 18 3.4 Genotyping of Rtl1 knockout mice 18 3.5 Expression of adjacent genes of Rtl1 in Rtl1 knockout mice 19 3.6 Survival rate and sex difference in Rtl1 knockout mice 20 3.7 Body weight and brain weight of Rtl1 knockout mice during development 20 3.8 Expression of HPG axis-related genes in Rtl1 knockout mice 21 3.9 Morphology difference of ovary between Rtl1 wildtype and knockout mice 22 Chapter 4. Discussion 23 4.1 Summary of results 23 4.2 Rtl1 imprinting status and isoform expression 24 4.3 Wdr25 may be up-and down-stream target of Rtl1 in the regulation of puberty 25 4.4 GnRH regulation and premature puberty 25 4.5 Limitation of this study 26 4.6 Contribution and possible application 26 Reference 64 TABLES AND FIGURES Figure 1. RTL1 expression in different organs of mice. 29 Figure 2. Different Rtl1 isoforms are expressed in different brain regions 33 Figure 3. miR-127 may be the major miRNA for regulating Rtl1 expression in different brain regions 35 Figure 4. Rtl1 expresses different isoforms but all paternally expressed in the pituitary gland and adrenal gland of HPA axis 37 Figure 5. Generation of Rtl1 knockout mice 39 Figure 6. Validation of Rtl1 knockout of Rtl1 knockout mice in DNA level 41 Figure 7. Validation of Rtl1 knockout of Rtl1 knockout mice in protein level 43 Figure 8. Expression of adjacent genes of Rtl1 in Rtl1 knockout mice 45 Figure 9. The ratio of each genotype in E15.5 embryo and p28 mice 47 Figure 10. Body weight and brain weight of Rtl1 knockout mice during development 49 Figure 11. Expression of HPG axis related genes in Rtl1 knockout mice 51 Figure 12. LH and FSH ELISA showed higher FSH level in Rtl1m+/p- mice in postnatal day 28 53 Figure 13. Morphology difference of ovary between Rtl1 wildtype and knockout mice 55 Supplementary Tables and figures 56 Figure S1. Confirmation of our RT-qPCR result for Rtl1 isoforms expression 57 Table S1. RT-qPCR primers for genes adjacent to Rtl1 58 Figure S2. Melt curve of RT-qPCR for genes adjacent to Rtl1 60 Table S2. RT-qPCR primers for HPG axis related genes 61 Figure S3. Melt curve of RT-qPCR for HPG axis related genes. 62 | - |
| dc.language.iso | en | - |
| dc.subject | 印記基因 | zh_TW |
| dc.subject | 下視丘－腦垂腺－腎上腺軸 | zh_TW |
| dc.subject | 下視丘－腦垂腺－性腺軸 | zh_TW |
| dc.subject | Rtl1 | zh_TW |
| dc.subject | 表觀遺傳學 | zh_TW |
| dc.subject | genomic imprinting | en |
| dc.subject | epigenetics | en |
| dc.subject | Retrotransposon-Like 1 | en |
| dc.subject | HPA axis | en |
| dc.subject | HPG axis | en |
| dc.title | 探索Rtl1於小鼠腦中的表現機制與功能 | zh_TW |
| dc.title | Investigating the mechanisms and functions of Rtl1 in the mouse brain | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林劭品;阮麗蓉;林甫容 | zh_TW |
| dc.contributor.oralexamcommittee | Shau-Ping Lin;Li-Jung Juan;Fu-Jung Lin | en |
| dc.subject.keyword | 表觀遺傳學,印記基因,Rtl1,下視丘－腦垂腺－性腺軸,下視丘－腦垂腺－腎上腺軸, | zh_TW |
| dc.subject.keyword | epigenetics,genomic imprinting,Retrotransposon-Like 1,HPA axis,HPG axis, | en |
| dc.relation.page | 71 | - |
| dc.identifier.doi | 10.6342/NTU201803389 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2018-08-15 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 腦與心智科學研究所 | - |
| dc.date.embargo-lift | 2028-08-14 | - |
| 顯示於系所單位： | 腦與心智科學研究所 | |
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