Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders:
Gespeichert in:
| Beteilige Person: | |
|---|---|
| Format: | Hochschulschrift/Dissertation Buch |
| Sprache: | Englisch |
| Veröffentlicht: |
Ulm
2018
|
| Schlagwörter: | |
| Links: | http://d-nb.info/1189458314/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031588865&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| Umfang: | 141 Blätter Illustrationen, Diagramme 30 cm |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV046209953 | ||
| 003 | DE-604 | ||
| 005 | 00000000000000.0 | ||
| 007 | t| | ||
| 008 | 191022s2018 gw a||| m||| 00||| eng d | ||
| 015 | |a 19,H08 |2 dnb | ||
| 016 | 7 | |a 1189458314 |2 DE-101 | |
| 020 | |c Broschur | ||
| 035 | |a (OCoLC)1125196011 | ||
| 035 | |a (DE-599)KXP1667630814 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c XA-DE-BW | ||
| 049 | |a DE-355 | ||
| 084 | |a 610 |2 sdnb | ||
| 084 | |a 570 |2 sdnb | ||
| 084 | |a 616.027 |2 sdnb | ||
| 100 | 1 | |a Lutz, Anne-Kathrin |e Verfasser |0 (DE-588)1188722190 |4 aut | |
| 245 | 1 | 0 | |a Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders |c Anne-Kathrin Lutz |
| 264 | 1 | |a Ulm |c 2018 | |
| 300 | |a 141 Blätter |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Universität Ulm |d 2018 | ||
| 653 | |a Neurodevelopmental Disorders | ||
| 653 | |a Genetics | ||
| 653 | |a Induced pluripotent stem cells | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u http://d-nb.info/1189458314/04 |3 Inhaltsverzeichnis |
| 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=031588865&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 943 | 1 | |a oai:aleph.bib-bvb.de:BVB01-031588865 | |
Datensatz im Suchindex
| _version_ | 1819378481238114304 |
|---|---|
| adam_text | T
ABLE
OF
C
ONTENTS
1
A
BBREVIATIONS
6
10
2
I
NTRODUCTION
2.1
AUTISM
SPECTRUM
DISORDERS
(ASD)
10
2.2
THE
SHANK
PROTEIN
FAMILY
12
2.2.1
PHYSIOLOGICAL
FUNCTION
12
2.2.2
IMPLICATION
OF
SHANKS
IN
DISEASE
14
2.2.3
PHELAN-MCDERMID
SYNDROME
15
2.2.4
SHANK
ANIMAL
MODELS
17
2.3
FORKHEAD
BOX
PROTEIN
G1
(FOXGL)
18
2.3.1
FOXG1
AND
ASD
18
2.3.2
FOXGL
FUNCTION
IN
HEALTH
AND
DISEASE
19
2.4
MYOGENIC
DEVELOPMENT
AND
MATURATION
21
2.4.1
DEVELOPMENT
AND
MATURATION
OF
MYOGENIC
CELLS
21
2.4.2
DEVELOPMENT
AND
MATURATION
OF
THE
NEUROMUSCULAR
JUNCTION
(NMJ)
24
2.4.3
SHANK
PROTEINS
IN
MYOGENIC
CELLS
25
2.5
HUMAN
INDUCED
PLURIPOTENT
STEM
CELLS
(HIPSCS)
26
2.5.1
HIPSCS
AS
MODEL
SYSTEM
26
2.5.2
INVESTIGATION
OF
SHANKS
IN
HIPSC
SYSTEMS
27
2.6
AIMS
OF
THIS
THESIS
29
3
M
ATERIAL
AND
M
ETHODS
31
3.1
MATERIAL
31
3.1.1
CHEMICALS
31
3.1.2
CONSUMABLES
33
3.1.3
CELL
CULTURE
CONSUMABLES
AND
MEDIA
33
3.1.4
KITS
37
3
3.1.5
PRIMERS
AND
DNA
CONSTRUCTS
37
3.1.6
ANTIBODIES
38
3.1.7 BUFFERS
AND
SOLUTIONS
40
3.1.8
EQUIPMENT
AND
LABWARE
41
3.1.9
SOFTWARE
42
3.2
METHODS
42
3.2.1
CELL
CULTURE
42
3.2.2
CRISPR/CAS9
45
3.2.3
RNA
AND
PROTEIN
ANALYSIS
48
3.2.4 ELECTRON
MICROSCOPY
52
3.2.5
IMAGE
ANALYSIS
52
3.2.6
STATISTICAL
ANALYSIS
53
4
R
ESULTS
54
4.1
PART
I:
SHANK2
DELETION
AFFECTS
FOXG1
EXPRESSION
AND
MGLURS
SIGNALING
54
4.1.1
GENERATION
OF
HIPSCS
FROM
A
SHANK2
DELETION
FAMILY
54
4.1.2
SHANK2
IS
SIGNIFICANTLY
REDUCED
IN
PATIENT-DERIVED
HIPSCS
AND
NEURONS
55
4.1.3
SCREEN
FOR
CHANGES
IN
SYNAPTIC
AND
ASD-RELATED
GENES
IN
SHANK2
DELETED
NEURONS
59
4.1.4
FOXG1
IS
SPECIFICALLY
UPREGULATED
IN
21
DAYS
OLD
NEURONS
62
4.1.5
FOXG1
UPREGULATION
CORRELATES
WITH
MORPHOLOGICAL
CHANGES,
CELL
CYCLE
PROGRESSION
AND
APOPTOTIC
LEVELS
IN
NEURONAL
CELLS
63
4.1.6
GLUTAMATERGIC
SIGNALING
IS
ALTERED
IN
SHANK2
DELETED
NEURONS
67
4.1.7
SYNAPTIC
ALTERATIONS
IN
SHANK2
DELETED
NEURONS
CAN
PARTIALLY
BE
RESCUED
BY
APPLICATION
OF
THE
POSITIVE
ALLOSTERIC
MGLURS
MODULATOR
CDPPB
71
4.2
PART
II:
SHANK3
MUTATIONS
IMPAIR
DEVELOPMENT
AND
MATURATION
OF
MOTOR
NEURONS,
MYOGENIC
CELLS
AND
NEUROMUSCULAR
JUNCTIONS
73
4.2.1
GENERATION
OF
A
HIPSC
LINE
OF
A
HYPOTONIC
PMDS
PATIENT
73
4.2.2
GENERATION
OF
A
HIPSC
LINE
HARBORING
A
SHANK3
STOP
MUTATION
(INSG)
USING
CRISPR/CAS9
74
4.2.3
SHANK3
EXPRESSION
IS
REDUCED
IN
HIPSCS
AND
MOTOR
NEURONS
OF
MUTATED
CELL
LINES
77
4.2.4
SHANK3
MUTATED
MOTOR
NEURONS
SHOW
MORPHOLOGICAL
ALTERATIONS
AND
SYNAPTIC
DEFICITS
79
4
4.2.5
MEDIUM
OF
SHANK3
MUTATED
MOTOR
NEURONS
INDUCES
LESS
MATURE
ENDPLATES
IN
MYOGENIC
CELLS
81
4.2.6
SHANK3
MUTATED
MOTOR
NEURONS
INDUCE
LESS
MATURE
ENDPLATES
IN
MYOGENIC
CELLS
84
4.2.7
SHANK3
MUTATED
MUSCLE
CELLS
SHOW
IMPAIRED
MYOGENIC
DIFFERENTIATION
AND
NMJ
MATURATION
86
4.2.8
SHANK3
LOCALIZES
TO
POST-SYNAPTIC
ACHR
CLUSTERS
IN
CO-CULTURES
90
4.2.9
SHANK3
LOCALIZES
TO
Z-DISCS
IN
SKELETAL
MUSCLE
SARCOMERES
90
4.2.10
SHANK3
MUTATIONS
ALTER
THE
ORGANIZATION
OF
MUSCLE
SARCOMERES
91
5
D
ISCUSSION
95
5.1
SHANK2
DELETION
AFFECTS
FOXG1
EXPRESSION
AND
MGLURS
SIGNALING
95
5.1.1
FOXG1
DEREGULATION
95
5.1.2
IMPAIRMENT
OF
GLUTAMATERGIC
SIGNALING
101
5.1.3
CONCLUSION
107
5.2
SHANK3
MUTATIONS
IMPAIR
DEVELOPMENT
AND
MATURATION
OF
MOTOR
NEURONS,
MYOGENIC
CELLS
AND
NEUROMUSCULAR
JUNCTIONS
108
5.2.1
NEURONAL
AND
SYNAPTIC
CHANGES
108
5.2.2
ENDPLATE
ALTERATIONS
112
5.2.3
DEFICIENT
MYOGENIC
MATURATION
115
5.2.4
SHANK3
IN
THE
SARCOMERE
118
5.2.5
CONCLUSION
119
6
S
UMMARY
121
7
R
EFERENCES
123
8
A
PPENDIX
133
9
S
TATUTORY
DECLARATION
139
10
P
EER
-
REVIEWED
PUBLICATIONS
140
11
A
CKNOWLEDGMENTS
141
5
|
| any_adam_object | 1 |
| author | Lutz, Anne-Kathrin |
| author_GND | (DE-588)1188722190 |
| author_facet | Lutz, Anne-Kathrin |
| author_role | aut |
| author_sort | Lutz, Anne-Kathrin |
| author_variant | a k l akl |
| building | Verbundindex |
| bvnumber | BV046209953 |
| ctrlnum | (OCoLC)1125196011 (DE-599)KXP1667630814 |
| discipline | Biologie Medizin |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01573nam a2200409 c 4500</leader><controlfield tag="001">BV046209953</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">t|</controlfield><controlfield tag="008">191022s2018 gw a||| m||| 00||| eng d</controlfield><datafield tag="015" ind1=" " ind2=" "><subfield code="a">19,H08</subfield><subfield code="2">dnb</subfield></datafield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">1189458314</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="c">Broschur</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1125196011</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)KXP1667630814</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="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">XA-DE-BW</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-355</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">610</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">570</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">616.027</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Lutz, Anne-Kathrin</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1188722190</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders</subfield><subfield code="c">Anne-Kathrin Lutz</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Ulm</subfield><subfield code="c">2018</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">141 Blätter</subfield><subfield code="b">Illustrationen, Diagramme</subfield><subfield code="c">30 cm</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">Universität Ulm</subfield><subfield code="d">2018</subfield></datafield><datafield tag="653" ind1=" " ind2=" "><subfield code="a">Neurodevelopmental Disorders</subfield></datafield><datafield tag="653" ind1=" " ind2=" "><subfield code="a">Genetics</subfield></datafield><datafield tag="653" ind1=" " ind2=" "><subfield code="a">Induced pluripotent stem cells</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="856" ind1="4" ind2="2"><subfield code="m">B:DE-101</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://d-nb.info/1189458314/04</subfield><subfield code="3">Inhaltsverzeichnis</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=031588865&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:BVB01-031588865</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV046209953 |
| illustrated | Illustrated |
| indexdate | 2024-12-20T18:46:07Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-031588865 |
| oclc_num | 1125196011 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | 141 Blätter Illustrationen, Diagramme 30 cm |
| publishDate | 2018 |
| publishDateSearch | 2018 |
| publishDateSort | 2018 |
| record_format | marc |
| spellingShingle | Lutz, Anne-Kathrin Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders |
| subject_GND | (DE-588)4113937-9 |
| title | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders |
| title_auth | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders |
| title_exact_search | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders |
| title_full | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders Anne-Kathrin Lutz |
| title_fullStr | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders Anne-Kathrin Lutz |
| title_full_unstemmed | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders Anne-Kathrin Lutz |
| title_short | Human induced pluripotent stem cell (hiPSC) culture systems as in vitro models for the analysis of SHANK mutations in neurodevelopmental disorders |
| title_sort | human induced pluripotent stem cell hipsc culture systems as in vitro models for the analysis of shank mutations in neurodevelopmental disorders |
| topic_facet | Hochschulschrift |
| url | http://d-nb.info/1189458314/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031588865&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT lutzannekathrin humaninducedpluripotentstemcellhipscculturesystemsasinvitromodelsfortheanalysisofshankmutationsinneurodevelopmentaldisorders |