ausblenden:
Sprache(n):
eng - English
Datum:
2018-072018-07
Publikationsstatus:
Erschienen
Seiten:
155
Ort, Verlag, Ausgabe:
Kiel : Christian-Albrechts-Universität
Inhaltsverzeichnis:
Contents
Summary ................................................................................................................................................. 9
Zusammenfassung ................................................................................................................................. 11
General introduction ............................................................................................................................. 14
Behavior and evolution ..................................................................................................................... 14
Mate choice ....................................................................................................................................... 14
Assortative mating ............................................................................................................................ 15
House mouse and paternal mate choice preference .......................................................................... 16
1-Competitive Ability .................................................................................................................... 17
2-Personality ................................................................................................................................. 18
3-Ultrasonic Vocalization ................................................................................................................. 18
Genomic imprinting .......................................................................................................................... 19
Genomic imprinting and brain development .................................................................................... 19
Imprinted gene and mate choice preference in house mouse ............................................................ 20
Aim of the project ............................................................................................................................. 22
Chapter1 ................................................................................................................................................ 24
Involvement of the Prader-Willi Syndrome (PWS) region genes in mouse behavior .......................... 24
Introduction ....................................................................................................................................... 25
Analysis of SNORD Copy Number Variation .................................................................................. 28
SNORD115 and 116 target genes ..................................................................................................... 30
Link between SNORD copy number and personality ....................................................................... 34
Correlation between SNORD115 and 116 copy numbers ................................................................ 42
Inheritance of SNORD copy numbers .............................................................................................. 45
SNORD copy number differences across tissues .............................................................................. 50
Variation of personality in inbred mice ............................................................................................ 51
SNORD copy number influence on the brain transcriptome ............................................................ 54
SNORD116 copy number and craniofacial features ......................................................................... 60
Differential gene expression through SNORD CNV ........................................................................ 64
Discussion ......................................................................................................................................... 66
SNROD115/ 116 CNV and personality ............................................................................................ 66
Correlation of personality and cognitive ability ............................................................................... 67
Correlation of personality and metabolism ....................................................................................... 68
Correlation of personality traits and vocalization ............................................................................. 68
Personality and craniofacial features ................................................................................................ 69
SNOD115/ 116 and the Prader-Willi syndrome ............................................................................... 69
6
Inheritance of SNROD115 and 116 .................................................................................................. 70
Mice sample ...................................................................................................................................... 71
Mouse keeping .................................................................................................................................. 71
Mouse dissection ............................................................................................................................... 71
DNA extraction ................................................................................................................................. 71
mRNA extraction and cDNA synthesis ............................................................................................ 72
RNAseq analysis ............................................................................................................................... 73
Small RNA extraction, cDNA synthesis, library preparation and sequencing ................................. 73
Read mapping ................................................................................................................................... 74
snoRNA analysis ............................................................................................................................... 75
Droplet digital PCR ........................................................................................................................... 75
1- Finding a suitable reference gene ............................................................................................ 76
2-Primer designing ....................................................................................................................... 76
3-DNA digestion and ddPCR ........................................................................................................ 77
4-Copy Number Calculation ......................................................................................................... 78
Mouse Personality ............................................................................................................................. 81
Behavioral Tests................................................................................................................................ 81
Elevated Plus Maze ........................................................................................................................... 81
Open Field ......................................................................................................................................... 81
Dark/Light Box ................................................................................................................................. 81
Statistical Analysis ............................................................................................................................ 83
Shape phenotyping ............................................................................................................................ 85
Chapter 2 ............................................................................................................................................... 90
Functional analysis of the paternally expressed gene Peg13 ................................................................ 90
Introduction ....................................................................................................................................... 91
Results ............................................................................................................................................... 93
Peg13 and Trappc9 Expression ........................................................................................................ 93
Peg13 expression in the brain ........................................................................................................... 96
Peg13 expression during developmental stages ................................................................................ 97
A possible PEG13 protein ................................................................................................................. 98
Generation of Knock-out mice .......................................................................................................... 99
Peg13 3’-knockout mouse .............................................................................................................. 101
Behavioral tests on Peg13 3’-region knockout mice ...................................................................... 102
RNAseq analysis on Peg13 3’- region knockout mice ................................................................... 108
GO analysis ..................................................................................................................................... 109
7
Discussion ....................................................................................................................................... 109
Expression of Peg13, Kcnk9 and Trappc9 are co-regulated ........................................................... 109
Peg13 is not a simple non-coding RNA .......................................................................................... 110
Behavior of Peg13 3’-region knockout mice .................................................................................. 110
Anxiety behavior of Peg13 3’-KO mice ......................................................................................... 111
Conclusion ...................................................................................................................................... 112
Material and Methods ..................................................................................................................... 113
RNAseq analysis across different tissues ........................................................................................ 113
Ribosomal profiling data analysis ................................................................................................... 113
Generation of knock-out mice by genOway ................................................................................... 113
Novel Object Test ........................................................................................................................... 114
Other procedures ............................................................................................................................. 114
General Discussion ............................................................................................................................. 116
The general background underlying this PhD thesis....................................................................... 116
The PWS region may be associated to the paternal mate choice preference in Western house mouse by regulating mouse personality ..................................................................................................... 117
Evolution of personality .................................................................................................................. 117
1-Selective Neutrality .................................................................................................................. 117
2-Mutation-selection balance ..................................................................................................... 118
3-Balancing Selection ................................................................................................................. 122
Personality and imprinting .............................................................................................................. 123
1-Different recombination rate between male and female .......................................................... 123
2-Co-adapted gene expression .................................................................................................... 123
Peg13 could be involved in sexual behavior in mouse ................................................................... 124
Conclusion .......................................................................................................................................... 126
Reference ............................................................................................................................................ 128
Acknowledgements ............................................................................................................................. 151
Contributions to the thesis .................................................................................................................. 153
Declaration .......................................................................................................................................... 154
Curriculum Vitae ................................................................................................................................ 155
Art der Begutachtung:
-
Identifikatoren:
Anderer: Diss/13099
Art des Abschluß:
Doktorarbeit
