Molecular analysis of skeletal malformations caused by mutations in BMP receptors:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Berlin
2014
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | VIII, 99 Blätter Illustrationen, Diagramme |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV042203645 | ||
| 003 | DE-604 | ||
| 005 | 20230119 | ||
| 007 | t | ||
| 008 | 141124s2014 a||| m||| 00||| eng d | ||
| 035 | |a (OCoLC)903693230 | ||
| 035 | |a (DE-599)BVBBV042203645 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-11 | ||
| 082 | 0 | |a 610 | |
| 084 | |a YB 3000 |0 (DE-625)153115:12905 |2 rvk | ||
| 100 | 1 | |a Deichsel, Alexandra Caroline Sooki |d 1980- |e Verfasser |0 (DE-588)106251632X |4 aut | |
| 245 | 1 | 0 | |a Molecular analysis of skeletal malformations caused by mutations in BMP receptors |c von Diplim-Biochemikerin Alexandra Caroline Sooki Deichsel (geb. Hannes) |
| 264 | 1 | |a Berlin |c 2014 | |
| 300 | |a VIII, 99 Blätter |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Humboldt-Universität zu Berlin |d 2014 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 776 | 0 | 8 | |i Reproduziert als |a Deichsel, Alexandra Caroline Sooki |t Molecular analysis of skeletal malformations caused by mutations in BMP receptors |d Ketsch bei Manheim : Mikroform Dissertation, 2014 |h 2 Mikrofiches |w (DE-604)BV042512959 |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027642478&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 943 | 1 | |a oai:aleph.bib-bvb.de:BVB01-027642478 | |
Datensatz im Suchindex
| _version_ | 1806055489787658240 |
|---|---|
| adam_text |
TABLE OF CONTENTS
TABLE OF CONTENTS
ABSTRACT ILL
ZUSAMMENFASSUNG IV
TABLE OF CONTENTS VI
1 INTRODUCTION 1
1.1 BMP SIGNALLING 1
1.2 SKELETAL MALFORMATIONS ASSOCIATED WITH MUTATIONS IN THE BMP
SIGNALLING PATHWAY 2
1.2.1 ACROMESOMELIC CHONDRODYSPLASIA 3
1.2.2 FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) 5
1.2.3 ENDOCHONDRAL OSSIFICATION 9
2 AIMS AND OBJECTIVES 13
3 MATERIALS AND METHODS 14
3.1 MATERIALS . 14
3.1.1 CHEMICALS 14
3.1.2 BUFFERS AND SOLUTIONS 14
3.1.3 ENZYMES 14
3.1.4 ANTIBODIES 14
3.1.5 BACTERIA 15
3.1.6 PLASMID VECTORS 15
3.1.7 DNA OLIGONUCLEOTIDES 17
3.1.8 KITS FOR MOLECULAR CLONING AND BIOCHEMISTRY 20
3.1.9 MEDIA, BUFFERS AND DISPOSABLES FOR CELL CULTURE WORK 20
3.1.10 CELL LINES 21
3.1.11 CHICKEN EMBRYOS '. 21
3.1.12 TECHNICAL EQUIPMENT 21
3.1.14 SOFTWARE AND DATABASES 24
3.3 METHODS 25
3.3.1 MOLECULAR BIOLOGY 25
3.3.2 CELL CULTURE TECHNIQUES 29
3.3.3 CELL STAINING TECHNIQUES 32
3.3.4 LUCIFERASE REPORTER ASSAYS 33
3.3.5 PROTEINBIOCHEMISTRY 34
HTTP://D-NB.INFO/1062889126
TABLE OF CONTENTS
3.3.6 SEQUENCE ALIGNMENT 36
3.3.7 STATISTICS 36
4 RESULTS 37
4.1 ACROMESOMELIC CHONDRODYSPLASIA IS CAUSED BY BMPR1B LOSS OF FUNCTION
MUTATIONS 37
4.1.1 HOMOZYGOUS BMPR1B MISSENSE AND NONSENSE MUTATIONS ASSOCIATED WITH
ACROMESOMELIC CHONDRODYSPLASIA TYPE GREBE 37
4.1.2 C53R AFFECTS A CONSERVED CYSTEINE IN THE LIGAND BINDING DOMAIN OF
BMPR1B 39
4.1.3 TRANSDUCTION OF GDF5 SIGNALS IS IMPAIRED IN BMPR1B P.(C53R) 41
4.1.4 THE EFFECT OF BMPR1B P.(C53R) DIFFERS FROM HETEROZYGOUS DOMINANT
NEGATIVE BMPR1B
MUTATIONS ASSOCIATED WITH BDA2 44
4.2 FOP IS CAUSED BY MUTATIONS IN ACVR1- COMPARISON OF THE RARE VARIANT
P.(Q207E) AND
RECURRENT MUTATION P.(R206H) WITH THE ENGINEERED CONSTITUTIVELY ACTIVE
MUTATION Q207D 46
4.2.1 P.(Q207E) MUTATION CAUSES A CLASSIC FOP PHENOTYPE 46
4.2.2 R206 AND Q207 ARE LOCATED IN THE GS DOMAIN OF ACVRI 47
4.2.3 ACVRI MUTATIONS Q207E AND R206H EXHIBIT A PROCHONDROGENIC EFFECT,
WHICH IS LESS
PRONOUNCED THAN THE EFFECT OF Q207D 48
4.2.4 ACVRI MUTATIONS Q207E AND R206H INDUCE HYPERACTIVATION OF SMAD
DEPENDENT BMP
SIGNALLING, WHICH IS LESS PRONOUNCED THAN THAT OF CONSTITUTIVE ACTIVE
Q207D 50
4.2.5 HYPERACTIVATION OF BMP SIGNALLING BY ACVRI MUTATIONS Q207E AND
R206H IS PARTIALLY
INDEPENDENT OF LIGAND BINDING 53
4.2.6 ACVRI HAS AN INHIBITING EFFECT ON BMPR1A AND BMPR1B INDUCED BMP
SIGNALLING 57
4.3 ESTABLISHMENT OF VIRAL LUCIFERASE REPORTERS TO ANALYSE SIGNALLING
PATHWAYS OF ENDOCHONDRAL
OSSIFICATION 61
4.3.1 CLONING OF VIRAL LUCIFERASE REPORTERS 61
4.3.2 ESTABLISHMENT OF A BMP RESPONSIVE GLUC REPORTER 61
4.3.3 ESTABLISHMENT OF A WNT RESPONSIVE GLUC REPORTER 65
4.3.4 ESTABLISHMENT OF A HEDGEHOG RESPONSIVE GLUC REPORTER 66
4.3.5 HEDGEHOG SIGNALLING DURING CHONDROGENIC DIFFERENTIATION IS NOT
INCREASED BY EXPRESSION
OF ACVRI VARIANTS 69
5 DISCUSSION 71
5.1 ACROMESOMELIC CHONDRODYSPLASIA TYPE GREBE IS CAUSED BY LOSS OF
BMPR1B SIGNALLING 71
5.2 FOP ASSOCIATED MUTATIONS P.(Q207E) AND P.(R206H) HYPERACTIVATE BMP
SIGNALLING BUT DO
NOT CONFER CONSTITUTIVE ACTIVITY TO ACVRI 74
5.2.1 WHY DOES Q207E BEHAVE SO DIFFERENTLY FROM Q207D? 74
5.2.2 ACVRI HAS A BALANCING ROLE ON BMP SIGNALLING WHICH IS IMPAIRED IN
FOP 77
TABLE OF CONTENTS
5.2.3 FUTURE RESEARCH DIRECTIONS FOR FOP 79
5.3 MONITORING SIGNALLING PATHWAYS DURING CHONDROGENIC DIFFERENTIATION
WITH THE HELP OF VIRAL
REPORTERS ENCODING FOR A SECRETED LUCIFERASE 81
5.3.1 PROOF OF CONCEPT 81
5.3.2 LIMITATIONS OF ENHANCERS SUITABLE FOR RCAN REPORTER VECTORS 82
5.3.3 STRATEGIES TO IMPROVE VIRAL LUCIFERASE REPORTERS 82
6 REFERENCES 84
APPENDIX 91
INDEX OF ABBREVIATIONS 91
INDEX OF FIGURES 92
INDEX OF TABLES 93
LIST OF PUBLICATIONS 95
SELBSTSTANDIGKEITSERKLARUNG 96
CURRICULUM VITAE 97
ACKNOWLEDGEMENTS 98 |
| any_adam_object | 1 |
| author | Deichsel, Alexandra Caroline Sooki 1980- |
| author_GND | (DE-588)106251632X |
| author_facet | Deichsel, Alexandra Caroline Sooki 1980- |
| author_role | aut |
| author_sort | Deichsel, Alexandra Caroline Sooki 1980- |
| author_variant | a c s d acs acsd |
| building | Verbundindex |
| bvnumber | BV042203645 |
| classification_rvk | YB 3000 |
| ctrlnum | (OCoLC)903693230 (DE-599)BVBBV042203645 |
| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>00000nam a2200000 c 4500</leader><controlfield tag="001">BV042203645</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20230119</controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">141124s2014 a||| m||| 00||| eng d</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)903693230</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV042203645</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-11</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">610</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">YB 3000</subfield><subfield code="0">(DE-625)153115:12905</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Deichsel, Alexandra Caroline Sooki</subfield><subfield code="d">1980-</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)106251632X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Molecular analysis of skeletal malformations caused by mutations in BMP receptors</subfield><subfield code="c">von Diplim-Biochemikerin Alexandra Caroline Sooki Deichsel (geb. Hannes)</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Berlin</subfield><subfield code="c">2014</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">VIII, 99 Blätter</subfield><subfield code="b">Illustrationen, Diagramme</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="b">Dissertation</subfield><subfield code="c">Humboldt-Universität zu Berlin</subfield><subfield code="d">2014</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="776" ind1="0" ind2="8"><subfield code="i">Reproduziert als</subfield><subfield code="a">Deichsel, Alexandra Caroline Sooki</subfield><subfield code="t">Molecular analysis of skeletal malformations caused by mutations in BMP receptors</subfield><subfield code="d">Ketsch bei Manheim : Mikroform Dissertation, 2014</subfield><subfield code="h">2 Mikrofiches</subfield><subfield code="w">(DE-604)BV042512959</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027642478&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="943" ind1="1" ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-027642478</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV042203645 |
| illustrated | Illustrated |
| indexdate | 2024-07-31T01:18:54Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027642478 |
| oclc_num | 903693230 |
| open_access_boolean | |
| owner | DE-11 |
| owner_facet | DE-11 |
| physical | VIII, 99 Blätter Illustrationen, Diagramme |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| record_format | marc |
| spelling | Deichsel, Alexandra Caroline Sooki 1980- Verfasser (DE-588)106251632X aut Molecular analysis of skeletal malformations caused by mutations in BMP receptors von Diplim-Biochemikerin Alexandra Caroline Sooki Deichsel (geb. Hannes) Berlin 2014 VIII, 99 Blätter Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Humboldt-Universität zu Berlin 2014 (DE-588)4113937-9 Hochschulschrift gnd-content Reproduziert als Deichsel, Alexandra Caroline Sooki Molecular analysis of skeletal malformations caused by mutations in BMP receptors Ketsch bei Manheim : Mikroform Dissertation, 2014 2 Mikrofiches (DE-604)BV042512959 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027642478&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Deichsel, Alexandra Caroline Sooki 1980- Molecular analysis of skeletal malformations caused by mutations in BMP receptors |
| subject_GND | (DE-588)4113937-9 |
| title | Molecular analysis of skeletal malformations caused by mutations in BMP receptors |
| title_auth | Molecular analysis of skeletal malformations caused by mutations in BMP receptors |
| title_exact_search | Molecular analysis of skeletal malformations caused by mutations in BMP receptors |
| title_full | Molecular analysis of skeletal malformations caused by mutations in BMP receptors von Diplim-Biochemikerin Alexandra Caroline Sooki Deichsel (geb. Hannes) |
| title_fullStr | Molecular analysis of skeletal malformations caused by mutations in BMP receptors von Diplim-Biochemikerin Alexandra Caroline Sooki Deichsel (geb. Hannes) |
| title_full_unstemmed | Molecular analysis of skeletal malformations caused by mutations in BMP receptors von Diplim-Biochemikerin Alexandra Caroline Sooki Deichsel (geb. Hannes) |
| title_short | Molecular analysis of skeletal malformations caused by mutations in BMP receptors |
| title_sort | molecular analysis of skeletal malformations caused by mutations in bmp receptors |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027642478&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT deichselalexandracarolinesooki molecularanalysisofskeletalmalformationscausedbymutationsinbmpreceptors |