Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien: = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English German |
| Veröffentlicht: |
Erlangen ; Nürnberg
Friedrich-Alexander-Universität Erlangen-Nürnberg
2018
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zusammenfassung in deutscher Sprache |
| Beschreibung: | 151 Seiten Illustrationen, Diagramme 21 cm |
Internformat
MARC
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| 100 | 1 | |a Nübler, Stefanie |d 1982- |0 (DE-588)1162978740 |4 aut | |
| 245 | 1 | 0 | |a Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien |b = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |c vorgelegt von Stefanie Nübler (geb. Diermeier) |
| 246 | 1 | 1 | |a On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| 264 | 1 | |a Erlangen ; Nürnberg |b Friedrich-Alexander-Universität Erlangen-Nürnberg |c 2018 | |
| 300 | |a 151 Seiten |b Illustrationen, Diagramme |c 21 cm | ||
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| 337 | |b n |2 rdamedia | ||
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| 500 | |a Zusammenfassung in deutscher Sprache | ||
| 502 | |b Dissertation |c Friedrich-Alexander-Universität Erlangen-Nürnberg |d 2018 | ||
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| 999 | |a oai:aleph.bib-bvb.de:BVB01-030486078 | ||
Datensatz im Suchindex
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|---|---|
| adam_text | TABLE OF CONTENTS
ZUSAMMENFASSUNG.............................................................................................................
1
ABSTRACT..............................................................................................................................
4
1
INTRODUCTION...............................................................................................................
9
2
BACKGROUND..............................................................................................................
14
2.1 SKELETAL MUSCLES: STRUCTURE, FUNCTION AND
AGING......................................................14
2.2 THE INTERMEDIATE FILAMENT PROTEIN DESMIN
.............................................................
26
2.3 THE MUSCLE LINKER PROTEIN DYSTROPHIN
.....................................................................
30
2.4 MYOPATHIES: DESR350P DESMINOPATHY AND DUCHENNE MUSCULAR
DYSTROPHY...........32
2.5 MULTIPHOTON
MICROSCOPY...........................................................................................36
2.6 FORCE TRANSDUCER TECHNOLOGIES TO MEASURE MUSCLE FORCE
.......................................
43
3 GOALS AND SPECIFIC AIMS OF THE
STUDY....................................................................47
4 METHODS AND
MATERIALS..........................................................................................
48
4.1
METHODS......................................................................................................................
48
4.1.1 MOUSE MODELS: DESR349P KNOCK-IN MICE AND
MDX MICE
.............................................
48
4.1.2 SINGLE SKELETAL MUSCLE FIBRE PREPARATION
..................................................................
51
4.1.3 SECTIONS OF SOL AND EDL WITH A CRYOSTAT AND A
VIBRATOME...................................55
4.1.4 IMMUNOHISTOCHEMISTRY AND FLUORESCENCE STAININGS
.................................................
56
4.1.5 MULTIPHOTON MICROSCOPY AND MORPHOMETRIC ANALYSIS OF MYOSIN AND
NUCLEI
.........
57
4.1.6 SDS-PAGE FOR WESTERN BLOTTING AND MHC DISTRIBUTIONS
........................................
61
4.1.7 COMBINED STRUCTURE-FORCE RECORDINGS
......................................................................
65
4.1.8 STATISTICAL
ANALYSIS.....................................................................................................72
4.2
MATERIALS.....................................................................................................................
74
5
RESULTS.......................................................................................................................
81
5.1 BODY MASS OF MICE, MASS OF SOL, EDL, 10 AND SINGLE FIBRE DIAMETERS
...............
81
5.2 COLLAGEN CONTENT IN SOL AND EDL SECTIONS AS INDICATOR OF FIBROSIS
....................
85
5.3 STRUCTURAL SHG ANALYSIS OF THE SINGLE FIBRE MYOSIN ARCHITECTURE
.........................
87
5.4 NUMBER AND MORPHOLOGY OF MYONUCLEI IN SINGLE DESR349P FIBRES
..........................
94
5.5 LOCALISATION AND INTENSITY OF DESMIN IN MUSCLE SECTIONS FROM SOL AND
EDL.... 98
5.6 PROTEIN EXPRESSION LEVEL OF WT AND MUTANT DESMIN IN SOL, EDL AND IO
MUSCLE
HOMOGENATES............................................................................................................100
5.7 MHC ISOFORM DISTRIBUTION IN SOL HOMOGENATES FROM DESR349P MICE
..............
102
5.8 COMBINED STRUCTURE-FORCE RECORDINGS IN SINGLE EDL FIBRES FROM YOUNG
WT AND
OLDER
MDX
MICE.........................................................................................................104
6
DISCUSSION................................................................................................................
112
6.1 STRUCTURAL RECORDINGS IN DESR349P
MICE..................................................................112
6.1.1 MUSCLE ATROPHY AND FIBROSIS ARE STRUCTURAL CONTRIBUTORS TO MUSCLE
WEAKNESS IN
MUTANT DESR349P
MICE................................................................................................112
6.1.2 STRUCTURAL SUBCELLULAR DEVIATIONS, QUANTIFIED AS CAS AND VO,
REFLECT AGING IN WT
MUSCLES AND PRE-AGED REMODELLING IN MUTANT DESR349P MICE
...................................
114
6.1.3 INCREASED NUCLEAR DENSITY IN HORN DESR349P MICE COULD BE DUE TO
VERY EARLY
REGENERATION
PROCESSES.............................................................................................
116
6.1.4 REDUCED CONTENT OF MUTANT DESMIN IN HORN MICE SUGGESTS
PATHOLOGICALLY
INCREASED DESMIN
TURNOVER.......................................................................................
117
6.1.5 HIGHER PROPORTION OF MHC I IN SOL FROM HORN DESR349P MICE COMPARED
TO WT
AND HET ANIMALS SUGGESTS PREMATURE AGING OR VERY EARLY REGENERATION
....................
118
6.1.6 DESR349P MICE SHOW SOME PARALLELS BUT ALSO MAJOR DIFFERENCES
COMPARED TO
MDX AND DESMIN KNOCK-OUT
MICE.............................................................................
119
6.1.7 SEDENTARY DESR349P MICE ARE ONLY SUITED TO A LIMITED EXTENT AS
MODEL SYSTEM
FOR HUMAN DESR350P DESMINOPATHIES
........................................................................
121
6.2 FORCE RECORDINGS WITH THE MORPHOMECH ON MDX AND WT MICE: CALIBRATING
SUBCELLULAR CYTOARCHITECTURE TO PROJECTED FORCE OUTPUT
.......................................
122
6.2.1 THE MORPHOMECH DETECTED DIFFERENCES IN CA2+ SENSITIVITY,
CA2+-DEPENDANT
MAXIMUM FORCE AND STRUCTURAL PARAMETERS BETWEEN MDX AND WT
MICE...................122
6.2.2 THE MORPHOMECH GAVE FIRST HINTS ON A CORRELATION BETWEEN
MORPHOMETRIC
PARAMETERS (CAS, VO) AND CA2+-DEPENDANT FORCE CHARACTERISTICS IN SINGLE
MUSCLE
FIBRES............................................................................................................
124
6.2.3 OPTIMISATION POTENTIAL OF THE
MORPHOMECH...........................................................126
7 CONCLUDING REMARKS AND
OUTLOOK......................................................................129
8
REFERENCES................................................................................................................130
9
ABBREVIATIONS..........................................................................................................145
10 OWN
PUBLICATIONS...................................................................................................
147
11
ACKNOWLEDGEMENTS................................................................................................
149
12 CURRICULUM
VITAE...................................................................................................
151
|
| any_adam_object | 1 |
| author | Nübler, Stefanie 1982- |
| author_GND | (DE-588)1162978740 |
| author_facet | Nübler, Stefanie 1982- |
| author_role | aut |
| author_sort | Nübler, Stefanie 1982- |
| author_variant | s n sn |
| building | Verbundindex |
| bvnumber | BV045095400 |
| ctrlnum | (OCoLC)1045840857 (DE-599)DNB1162978511 |
| discipline | Biologie |
| format | Thesis Book |
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| language | English German |
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| physical | 151 Seiten Illustrationen, Diagramme 21 cm |
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| spelling | Nübler, Stefanie 1982- (DE-588)1162978740 aut Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies vorgelegt von Stefanie Nübler (geb. Diermeier) On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies Erlangen ; Nürnberg Friedrich-Alexander-Universität Erlangen-Nürnberg 2018 151 Seiten Illustrationen, Diagramme 21 cm txt rdacontent n rdamedia nc rdacarrier Zusammenfassung in deutscher Sprache Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2018 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030486078&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Nübler, Stefanie 1982- Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| subject_GND | (DE-588)4113937-9 |
| title | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| title_alt | On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| title_auth | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| title_exact_search | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| title_full | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies vorgelegt von Stefanie Nübler (geb. Diermeier) |
| title_fullStr | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies vorgelegt von Stefanie Nübler (geb. Diermeier) |
| title_full_unstemmed | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies vorgelegt von Stefanie Nübler (geb. Diermeier) |
| title_short | Quantifizierung strukturbasierter Muskelschwäche bei hereditären Myopathie-Modellen der Maus für humane Desminopathie und Duchenne Muskeldystrophie unter Verwendung neuartiger optisch-biomechatronischer Technologien |
| title_sort | quantifizierung strukturbasierter muskelschwache bei hereditaren myopathie modellen der maus fur humane desminopathie und duchenne muskeldystrophie unter verwendung neuartiger optisch biomechatronischer technologien on the structure function relationship to explain muscle weakness in inherited myopathies using murine models of duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| title_sub | = On the structure-function relationship to explain muscle weakness in inherited myopathies using murine models of Duchenne muscular dystrophy using novel optical multiphoton and biomechatronics technologies |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030486078&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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