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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃憲松(Hsien-Sung Huang) | |
dc.contributor.author | Dhivya Appan | en |
dc.contributor.author | 賴文雅 | zh_TW |
dc.date.accessioned | 2021-06-17T06:59:20Z | - |
dc.date.available | 2021-02-23 | |
dc.date.copyright | 2021-02-23 | |
dc.date.issued | 2021 | |
dc.date.submitted | 2021-01-25 | |
dc.identifier.citation | 1 Tucci, V. et al. Genomic Imprinting and Physiological Processes in Mammals. Cell 176, 952-965, doi:https://doi.org/10.1016/j.cell.2019.01.043 (2019). 2 Fundele, R. H. Surani, M. A. Experimental embryological analysis of genetic imprinting in mouse development. Dev Genet 15, 515-522, doi:10.1002/dvg.1020150610 (1994). 3 Ferguson-Smith, A. C. Genomic imprinting: the emergence of an epigenetic paradigm. Nature Reviews Genetics 12, 565-575, doi:10.1038/nrg3032 (2011). 4 MacDonald, W. A. Epigenetic Mechanisms of Genomic Imprinting: Common Themes in the Regulation of Imprinted Regions in Mammals, Plants, and Insects. Genetics Research International 2012, 585024, doi:10.1155/2012/585024 (2012). 5 Yamasaki, K. et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Human Molecular Genetics 12, 837-847, doi:10.1093/hmg/ddg106 (2003). 6 Haig, D. Graham, C. Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell 64, 1045-1046, doi:10.1016/0092-8674(91)90256-x (1991). 7 Moore, T. Haig, D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 7, 45-49, doi:10.1016/0168-9525(91)90230-n (1991). 8 Logan, R. W. et al. High-precision genetic mapping of behavioral traits in the diversity outbred mouse population. Genes, brain, and behavior 12, 424-437, doi:10.1111/gbb.12029 (2013). 9 Flint, J. Analysis of quantitative trait loci that influence animal behavior. J Neurobiol 54, 46-77, doi:10.1002/neu.10161 (2003). 10 Franklin, T. B. et al. Epigenetic Transmission of the Impact of Early Stress Across Generations. Biological Psychiatry 68, 408-415, doi:https://doi.org/10.1016/j.biopsych.2010.05.036 (2010). 11 Dietz, D. M. et al. Paternal Transmission of Stress-Induced Pathologies. Biological Psychiatry 70, 408-414, doi:https://doi.org/10.1016/j.biopsych.2011.05.005 (2011). 12 Morgan, H. D., Sutherland, H. G. E., Martin, D. I. K. Whitelaw, E. Epigenetic inheritance at the agouti locus in the mouse. Nature Genetics 23, 314-318, doi:10.1038/15490 (1999). 13 Crews, D. et al. Transgenerational epigenetic imprints on mate preference. Proceedings of the National Academy of Sciences 104, 5942-5946, doi:10.1073/pnas.0610410104 (2007). 14 Ng, S.-F. et al. Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring. Nature 467, 963-966, doi:10.1038/nature09491 (2010). 15 Meaney, M. J., Szyf, M. Seckl, J. R. Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends in Molecular Medicine 13, 269-277, doi:https://doi.org/10.1016/j.molmed.2007.05.003 (2007). 16 Dias, B. G. Ressler, K. J. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature neuroscience 17, 89-96, doi:10.1038/nn.3594 (2014). 17 Jiang, Y.-h. et al. Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation. Neuron 21, 799-811, doi:https://doi.org/10.1016/S0896-6273(00)80596-6 (1998). 18 Colas, D., Wagstaff, J., Fort, P., Salvert, D. Sarda, N. Sleep disturbances in Ube3a maternal-deficient mice modeling Angelman syndrome. Neurobiology of Disease 20, 471-478, doi:https://doi.org/10.1016/j.nbd.2005.04.003 (2005). 19 Champagne, F. A., Curley, J. P., Swaney, W. T., Hasen, N. S. Keverne, E. B. Paternal influence on female behavior: the role of Peg3 in exploration, olfaction, and neuroendocrine regulation of maternal behavior of female mice. Behav Neurosci 123, 469-480, doi:10.1037/a0015060 (2009). 20 Peall, K. J. et al. SGCE mutations cause psychiatric disorders: clinical and genetic characterization. Brain 136, 294-303, doi:10.1093/brain/aws308 (2013). 21 Yokoi, F., Dang, M. T., Li, J. Li, Y. Myoclonus, Motor Deficits, Alterations in Emotional Responses and Monoamine Metabolism in ε-Sarcoglycan Deficient Mice. The Journal of Biochemistry 140, 141-146, doi:10.1093/jb/mvj138 (2006). 22 Zhang, L., Yokoi, F., Parsons, D. S., Standaert, D. G. Li, Y. Alteration of Striatal Dopaminergic Neurotransmission in a Mouse Model of DYT11 Myoclonus-Dystonia. PLOS ONE 7, e33669, doi:10.1371/journal.pone.0033669 (2012). 23 Benarroch, E. E. Locus coeruleus. Cell Tissue Res 373, 221-232, doi:10.1007/s00441-017-2649-1 (2018). 24 Marino, M. D., Bourdélat-Parks, B. N., Cameron Liles, L. Weinshenker, D. Genetic reduction of noradrenergic function alters social memory and reduces aggression in mice. Behavioural Brain Research 161, 197-203, doi:https://doi.org/10.1016/j.bbr.2005.02.005 (2005). 25 Burgess, Christian R. Peever, John H. A Noradrenergic Mechanism Functions to Couple Motor Behavior with Arousal State. Current Biology 23, 1719-1725, doi:https://doi.org/10.1016/j.cub.2013.07.014 (2013). 26 Sara, Susan J. Bouret, S. Orienting and Reorienting: The Locus Coeruleus Mediates Cognition through Arousal. Neuron 76, 130-141, doi:https://doi.org/10.1016/j.neuron.2012.09.011 (2012). 27 Berridge, C. W., Stratford, T. L., Foote, S. L. Kelley, A. E. Distribution of dopamine beta-hydroxylase-like immunoreactive fibers within the shell subregion of the nucleus accumbens. Synapse 27, 230-241, doi:10.1002/(sici)1098-2396(199711)27:3<230::Aid-syn8>3.0.Co;2-e (1997). 28 Moloney, R. D., Dinan, T. G. Cryan, J. F. Strain-dependent variations in visceral sensitivity: relationship to stress, anxiety and spinal glutamate transporter expression. Genes Brain Behav 14, 319-329, doi:10.1111/gbb.12216 (2015). 29 Bothe, G. W., Bolivar, V. J., Vedder, M. J. Geistfeld, J. G. Behavioral differences among fourteen inbred mouse strains commonly used as disease models. Comp Med 55, 326-334 (2005). 30 van Gaalen, M. M. Steckler, T. Behavioural analysis of four mouse strains in an anxiety test battery. Behavioural Brain Research 115, 95-106, doi:https://doi.org/10.1016/S0166-4328(00)00240-0 (2000). 31 Crawley, J. N. et al. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology 132, 107-124, doi:10.1007/s002130050327 (1997). 32 Au - You, R., Au - Liu, Y. Au - Chang, R. C.-C. A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice. JoVE, e58973, doi:doi:10.3791/58973 (2019). 33 Gorina, Y. V. et al. The battery of tests for experimental behavioral phenotyping of aging animals. Advances in Gerontology 7, 137-142, doi:10.1134/S2079057017020060 (2017). 34 van Gaalen, M. M. Steckler, T. Behavioural analysis of four mouse strains in an anxiety test battery. Behav Brain Res 115, 95-106, doi:10.1016/s0166-4328(00)00240-0 (2000). 35 Szabadi, E. Functional neuroanatomy of the central noradrenergic system. Journal of Psychopharmacology 27, 659-693, doi:10.1177/0269881113490326 (2013). 36 Benarroch, E. E. The locus ceruleus norepinephrine system. Neurology 73, 1699, doi:10.1212/WNL.0b013e3181c2937c (2009). 37 Lin, C.-Y. et al. Analysis of Genome-Wide Monoallelic Expression Patterns in Three Major Cell Types of Mouse Visual Cortex Using Laser Capture Microdissection. PLOS ONE 11, e0163663, doi:10.1371/journal.pone.0163663 (2016). 38 Lin, C. Y. et al. Analysis of Genome-Wide Monoallelic Expression Patterns in Three Major Cell Types of Mouse Visual Cortex Using Laser Capture Microdissection. PLoS One 11, e0163663, doi:10.1371/journal.pone.0163663 (2016). 39 Hsu, C. L. et al. Analysis of experience-regulated transcriptome and imprintome during critical periods of mouse visual system development reveals spatiotemporal dynamics. Hum Mol Genet 27, 1039-1054, doi:10.1093/hmg/ddy023 (2018). 40 Bolger, A. M., Lohse, M. Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114-2120, doi:10.1093/bioinformatics/btu170 (2014). 41 Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15-21, doi:10.1093/bioinformatics/bts635 (2013). 42 Trapnell, C. et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28, 511-515, doi:10.1038/nbt.1621 (2010). 43 Szklarczyk, D. et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 45, D362-D368, doi:10.1093/nar/gkw937 (2017). 44 Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102, 15545-15550, doi:10.1073/pnas.0506580102 (2005). 45 Mootha, V. K. et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34, 267-273, doi:10.1038/ng1180 (2003). 46 Aken, B. L. et al. The Ensembl gene annotation system. Database (Oxford) 2016, doi:10.1093/database/baw093 (2016). 47 Karolchik, D. et al. The UCSC Table Browser data retrieval tool. Nucleic Acids Res 32, D493-496, doi:10.1093/nar/gkh103 (2004). 48 Tyner, C. et al. The UCSC Genome Browser database: 2017 update. Nucleic Acids Res 45, D626-D634, doi:10.1093/nar/gkw1134 (2017). 49 Edgar, R., Domrachev, M. Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30, 207-210, doi:10.1093/nar/30.1.207 (2002). 50 Fisher, S. P. et al. Rapid assessment of sleep-wake behavior in mice. J Biol Rhythms 27, 48-58, doi:10.1177/0748730411431550 (2012). 51 Moloney, R. D., Dinan, T. G. Cryan, J. F. Strain-dependent variations in visceral sensitivity: relationship to stress, anxiety and spinal glutamate transporter expression. Genes, Brain and Behavior 14, 319-329, doi:10.1111/gbb.12216 (2015). 52 Leger, M. et al. Object recognition test in mice. Nature Protocols 8, 2531-2537, doi:10.1038/nprot.2013.155 (2013). 53 Raudvere, U. et al. g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Research 47, W191-W198, doi:10.1093/nar/gkz369 (2019). 54 Eden, E., Navon, R., Steinfeld, I., Lipson, D. Yakhini, Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics 10, 48, doi:10.1186/1471-2105-10-48 (2009). 55 Loos, M. et al. Sheltering Behavior and Locomotor Activity in 11 Genetically Diverse Common Inbred Mouse Strains Using Home-Cage Monitoring. PLOS ONE 9, e108563, doi:10.1371/journal.pone.0108563 (2014). 56 Wahlsten, D., Metten, P. Crabbe, J. C. A rating scale for wildness and ease of handling laboratory mice: results for 21 inbred strains tested in two laboratories. Genes, Brain and Behavior 2, 71-79, doi:10.1034/j.1601-183X.2003.00012.x (2003). 57 Salari, A.-A., Samadi, H., Homberg, J. R. Kosari-Nasab, M. Small litter size impairs spatial memory and increases anxiety- like behavior in a strain-dependent manner in male mice. Scientific Reports 8, 11281, doi:10.1038/s41598-018-29595-0 (2018). 58 Priebe, K. et al. Maternal influences on adult stress and anxiety-like behavior in C57BL/6J and BALB/cJ mice: A cross-fostering study. Developmental Psychobiology 47, 398-407, doi:10.1002/dev.20098 (2005). 59 Champagne, F. A., Curley, J. P., Keverne, E. B. Bateson, P. P. G. Natural variations in postpartum maternal care in inbred and outbred mice. Physiology Behavior 91, 325-334, doi:https://doi.org/10.1016/j.physbeh.2007.03.014 (2007). 60 Calatayud, F., Coubard, S. Belzung, C. Emotional reactivity in mice may not be inherited but influenced by parents. Physiology Behavior 80, 465-474, doi:https://doi.org/10.1016/j.physbeh.2003.10.001 (2004). 61 Bannister, A. J. Kouzarides, T. Regulation of chromatin by histone modifications. Cell Research 21, 381-395, doi:10.1038/cr.2011.22 (2011). 62 Wang, Z. et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nature Genetics 40, 897-903, doi:10.1038/ng.154 (2008). 63 Min, H., Lee, J.-Y. Kim, M. H. Hoxc gene collinear expression and epigenetic modifications established during embryogenesis are maintained until after birth. Int J Biol Sci 9, 960-965, doi:10.7150/ijbs.6739 (2013). 64 Mallo, M. Alonso, C. R. The regulation of Hox gene expression during animal development. Development 140, 3951, doi:10.1242/dev.068346 (2013). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72450 | - |
dc.description.abstract | 基因組印記是後代基因表達中受特定親代來源影響的現象。基因組印記的衝突理論指出,具有母系偏好的基因表達會促進出生體重的降低、成體大腦的縮小,以及較具有同情心和不自戀的性格,從而對母親的需求減少。在具有父系偏好的基因表達中將發生相反的情況。為了進一步探討親代基因組對後代行為產生的影響,我們想了解在分子、行為和電生理的層次上,親代基因組對其後代的影響。為此我們使用了兩個不同的小鼠品系:CAST / EiJ和C57BL / 6以及它們的正向(F1i)和反向(F1r)雜交的F1雜種。在行為方面,我們進行了學習、記憶,以及與焦慮和壓力相關的測試,以評估整體心理健康狀況。我們還進行了數種感覺與運動測試,以評估小鼠的整體身體健康狀況。我們在行為測試中觀察到雜種小鼠的異質遺傳,並在睡眠-覺醒模式、社交、焦慮和壓力反應中觀察到不同的遺傳模式。兒茶酚胺去甲腎上腺素(NE)有助於調節上述行為。 因此,我們檢查了不同大腦區域中兒茶酚胺合成中的限速酶酪氨酸氫氧化物(TH)的水平,發現四隻小鼠腦幹中TH的差異表達。 由於位於腦幹的藍斑軌跡(LC)是大腦NE的主要生產中心,因此我們決定研究小鼠LC神經元電特性的差異,這可能會導致雜種小鼠的行為差異。 我們觀察到雜種小鼠的放電特性與其親本菌株不同,這可能是影響小鼠之間行為差異的因素。B6、CAST、F1i和F1r小鼠全腦的RNA定序分析和GO分析證實了我們觀察到的某些行為。此外,我們進行了雜交小鼠大腦皮層的興奮神經元和星形膠質細胞的RNA定序分析。我們使用生物資訊學工具分析數據,製作了特定細胞類型中潛在印跡基因的列表,並確定了四個新的細胞類型特異性印跡基因。我們的跨學科工作使我們能夠欣賞雜種基因組的複雜性以及親代基因組對後代表現型的貢獻 | zh_TW |
dc.description.abstract | Genomic imprinting is the phenomenon of a parent of origin-specific influence in the gene expression of the offspring. The conflict theory of genomic imprinting states that a maternal bias in gene expression promotes lower birth weight, smaller adult brain and an empathizing and less narcissistic personality causing fewer demands on the mother. The opposite would occur for gene expression with a paternal bias. To explore this theme of parental genome affecting offspring behavior further, we wanted to look at the molecular, behavior, and electrophysiological level of effects of parental genomes on their offsprings. To do this, we used two distinct mouse sub-strains: CAST/EiJ and C57BL/6 and the resultant F1 hybrid of their initial (F1i) and reciprocal (F1r) cross. In the behavior front, we performed learning, memory, and anxiety stress-related tests to evaluate the overall mental health. We additionally performed several sensorimotor tests to assess the overall physical health of the mice. We observe heterotic inheritance in the hybrid mice in physical tests and different patterns of inheritance in sleep-wake patterns, social, anxiety and stress response. The catecholamine Norepinephrine (NE) helps regulate the abovementioned behaviors. Hence, we checked the levels of Tyrosine hydroxide (TH), the rate limiting enzyme in catecolamine synthesis, in different brain regions and found differential expression of TH in the brainstem of the four mice. Since Locus coeruleus (LC), located in the brainstem, is the major production centre of NE in the brain, we decided to investigate the differences in electric properties of LC neurons in the mice that could contribute to the differential behavior by the hybrid mice. We observe that the firing properties of the hybrid mice are different than their parental strains, which could be an influencing factor in the behavioral differences between the mice. RNA-seq and GO analysis of the whole-mouse-brain of B6, CAST, F1i, and F1r mice corroborated to some of the behaviors we observed. In addition, we performed RNA-seq of the Excitatory neurons and astrocytes cells of cortex of the hybrid mouse brain. We analyzed the data using bioinformatics tools and generated a list of potentially imprinted genes in specific cell types and have identified four novel cell-type-specific imprinted genes. Our multidisciplinary work allows us to appreciate the complex nature of the hybrid genome and the parental genome's contribution to the offsprings’ phenotype. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T06:59:20Z (GMT). No. of bitstreams: 1 U0001-1501202116313500.pdf: 3798973 bytes, checksum: 896c2a951a5e746899d8ce88a5500aca (MD5) Previous issue date: 2021 | en |
dc.description.tableofcontents | Contents 1. Introduction 1 1.1. Genomic Imprinting 1 1.2. Conflict theory of genomic imprinting 2 1.3. Role of Imprinted genes in mouse behavior 2 1.4. Noradrenergic system and mouse behavior 3 1.5. Locus Coeruleus 4 1.6. Knowledge gap 4 2. Materials and methods 7 2.1. Animals 7 2.2. Genotyping 7 2.3. Behavior tests 9 2.3.1. Test groups 9 2.3.2. Testing procedures 9 2.4. Western blot 13 2.5. Electrophysiology 14 2.6. Cell sorting 15 2.7. RNA-Seq 16 2.7.1. Cell-type-specific RNA-Seq 16 Imprinting Analysis 17 RT-qPCR 17 2.7.2. RNA-Seq of the behavior mice 18 2.8. Gene ontology and pathway analysis 18 3. Results 20 3.1. Differences in general behaviors of B6, CAST, F1i, and F1r mice 20 3.1.1. Differential brain and body weights of B6, CAST, F1i, and F1r mice 20 3.1.2. CAST mice have lower reproductive frequency 21 3.1.3. Differences in home cage behaviors of B6, CAST, F1i, and F1r mice 21 3.1.4. Hybrid mice display superior motor capacity 22 3.2. Sensory functions 23 3.3. Hybrid mice display a strain-specific effect in the anxiety paradigm and repetitive behavior 23 3.4. Hybrids display an intermediary effect in depression-like behavior 24 3.5. Hybrids have impaired long-term memory 24 3.6. Hybrids are socially more dominant but less sociable 25 3.7. GO analysis reveals higher enrichment of metabolic pathways in CAST mice 25 3.8. Cell-type-specific genomic imprinting of four genes in astrocytes and excitatory neurons 26 3.9. CAST mice have relatively higher TH expression in Brainstem 26 3.10. Locus coeruleus neurons in CAST, F1i and F1r display differential action potential properties compared to B6 27 4. Discussion 29 4.1. Key findings 29 4.2. Disputes and similarities with prior research 30 4.3. Limitations in technique and design 31 4.4. Implication and significance 31 4.5. Future direction 32 5. Figures and Figure legends 34 References 80 Appendix 84 Introduction 84 Materials and Methods 85 Chromatin Immunoprecipitation (ChIP) 85 Results 86 Discussion 87 | |
dc.language.iso | en | |
dc.title | 全面分析親代基因組對小鼠大腦的影響 | zh_TW |
dc.title | Comprehensive analyses of the impact of parental genomes in the mouse brain | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林劭品(Shau-Ping Lin),閔明源(Ming-Yuan Min),姚皓傑(Hau-Jie Yau) | |
dc.subject.keyword | 神經科學,表觀遺傳學,藍斑核,基因組印記,小鼠行為,親代基因組對後代大腦的影響,雜種小鼠, | zh_TW |
dc.subject.keyword | Neuroscience,Epigenetics,Locus Coeruleus,Genomic imprinting,mouse behavior,parental genome effects on offspring brain,hybrid mice, | en |
dc.relation.page | 89 | |
dc.identifier.doi | 10.6342/NTU202100068 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2021-01-25 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
顯示於系所單位: | 腦與心智科學研究所 |
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