Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants
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| 008 | 150722s2015 xx ad|| m||| 00||| eng d | ||
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| 100 | 1 | |a Lee, Sze Chim |e Verfasser |0 (DE-588)1070544779 |4 aut | |
| 245 | 1 | 0 | |a Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants |c vorgelegt von Sze Chim Lee |
| 264 | 1 | |c 2015 | |
| 300 | |a 99, 12 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |a Tübingen, Univ., Diss., 2015 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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Datensatz im Suchindex
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| adam_text | DIFFERENCES IN SOUND PROCESSING UPON GENETIC MUTATIONS IN
EPITHELIAL OR NEURONAL TISSUES BY COMPARING HETEROTRIMERIC
G-PROTEIN AND L-TYPE VOLTAGE GATED CALCIUM CHANNEL CA
V
1.2
MICE MUTANTS
DISSERTATION
DER MATHEMATISCH-NATURWISSENSCHAFTLICHEN FAKULTIT
DER EBERHARD KARTS UNIVERSITAT TUBINGEN
ZUR ERIANGUNG DES GRADES EINES
DOKTORS DER NATURWISSENSCHAFTEN
(OR. RER. NAT.)
VORGELEGT VON
SZE CHIM LEE
AUS HONG KONG,CHINA
TUBINGEN
2015
HTTP://D-NB.INFO/1071659847
CONTENTS
1. INTRODUCTION 10
1.1 ANATOMY AND SIGNAL TRANSDUCTION OF THE
COCHLEA 10
1.1.1 THE COCHLEA
AND ORGAN OF CORTI 11
1.17 HAIR CELLS AND THE SENSORY
TRANSDUCTION PROCESS 13
1.1.3 AUDITORY NERVE (AN)
FIBERS AND THEIR INNERVATIONS TO THE HAIR CELLS 17
1.2 THE ASCENDING AUDITORY PATHWAY 18
1.2.1 COCHLEAR NUCLEUS (CN) 18
1.2.2 THE SUPERIOR
OLIVARY COMPLEX (SOC) 18
1.2.3 THE LATERAL LEMNISCUS
(LL) AND THE NUCLEI
OF THE LATERAL LEMNISCUS
(NLL) 19
1.2.4 THE INFERIOR COLLICULUS
(IC) 20
12.5 THE MEDIAL GENICULATE BODY (MGB) 20
1.2.6 THE AUDITORY
CORTEX (AC) 20
1.3 THE ROLE OF G-PROTEIN SIGNALING
PATHWAY IN THE AUDITORY SYSTEM 20
1.3.1 HETEROTRIMERIC G-PROTEINS 20
1.3.2 G-PROTEIN SIGNALING PATHWAY AND
COCHLEAR DEVELOPMENT 22
1.4 THE ROLE OF L-TYPE VOLTAGE-GATED CA
2+
CHANNELS (L-VGCCS) CAVL.2 IN THE AUDITORY
SYSTEM 24
1.4.1 L-VGCCS CAVL.2 24
1.4.2 CAVL.2 IN THE AUDITORY SYSTEM 25
1.5 AIM OF STUDY 27
2. MATERIALS AND METHODS.. ....... ... 28
2.1 ANIMALS AND
CARE 28
2.2 GENERATION OF CAVL
.2 MICE MUTANTS 28
2.2.1 MICE MUTANTS WITH DELETION OF CAVL.2 IN THE AUDITORY PERIPHERY 28
2.2.2 MICE MUTANTS WITH DELETION
OF CAVL
.2 IN THE BRAINSTEM 28
2.3 GENERATION OF GAJ
AND MPINS MICE MUTANTS 29
2.3.1 MICE MUTANTS WITH GLOBAL DELETION
OF GAA OR GAU 29
2.3.2 MICE MUTANTS WITH
CONDITIONAL DELETION OF EITHER GAA OR GAA...................... 29
2.3.3 MICE MUTANTS WITH
CONDITIONAL DELETION OF BOTH GAA AND GAG 30
2.3.4 MICE MUTANTS WITH CONDITIONAL
DELETION OF MPINS 30
S
2.4 HEARING MEASUREMENTS 30
2.4.1 AUDITORY BRAINSTEM RESPONSES (ABR) MEASUREMENTS 30
2.4.2 DISTORTION PRODUCT OTOACOUSTIC
EMISSION (DPOAE) MEASUREMENTS 34
2.5 ABR WAVE ANALYSES 34
2.6 TISSUE PREPARATION 37
2.7 IMMUNOHISTOCHEMISTRY 37
2.8 RNA ISOLATION, CDNA SYNTHESIS AND REAL TIME PCR 38
2.9 PROTEIN ISOLATION
AND WESTERN BLOT 39
2.10 STATISTICAL ANALYSIS 39
5. RESULTS........... ......*........*...... ..... ..... .... .....
........ ...... 42
3.1 EXPRESSION OF GOA AND GOB ISOFORMS IN ADULT
MOUSE COCHLEA 42
3.1.1 GAS IS EXPRESSED IN NEUROFILAMENTS INNERVATING THE IHCS AND IN THE
SGNS 42
3.1.2 GAI3 IS SPECIFICALLY EXPRESSED IN HAIR CELLS, SUPPORTING
CELLS, AND THE
VM* NERVES .42
3.2. HEARING FUNCTION IN ADULT GLOBAL GAG, GAG, CONDITIONAL GAG, GAY,
CONDITIONAL
GOAGATT, AND CONDITIONAL MPINS MOUSE LINES 44
3.2.1 GOO BUT NOT GAG ALONE IS REQUIRED FOR NORMAL HEARING THRESHOLDS 44
3.2.2 CONDITIONAL GA^GOU AND MPINS KO MICE ARE SEVERELY HEARING IMPAIRED
47
3.2.3 CONDITIONAL GAAGAA AND MPINS KO MICE SHOW CIRCLING BEHAVIOR 48
3.2.4 DPOAE IN GLOBAL AND CONDITIONAL
GAA, GAU MOUSE LINES 48
3.2.5 GAA KO MICE HAVE PROGRESSIVE LOSS OF HEARING THRESHOLDS
OVER AGE 51
3.2.6 GDI3 KO MICE HAVE REDUCED SOUND-EVOKED NEURAL RESPONSES FROM AN
FIBERS S3
3.2.7 GNU KO MICE HAVE REDUCED SOUND-EVOKED NEURAL RESPONSES FROM HIGHER
AUDITOIY
CENTRES 55
3.2.8 CONDITIONAL GAU BUT NOT GLOBAL GOQ KO MICE HAVE ELEVATED CENTRAL
COMPENSATORY
RESPONSES SUBSEQUENT TO REDUCED PERIPHERAL INPUT 58
3.3 MOLECULAR PHENOTYPES RELATED TO THE FUNCTIONAL PHENOTYPES OF ADULT
GLOBAL GOA, GAU,
CONDITIONAL GAA, GAU, CONDITIONAL GAAGAA, AND CONDITIONAL MPINS MOUSE
LINES 59
3.3.1 LOSS OF GAU DOES
NOT ALTER THE EXPRESSION
OF PRESTIN AND KCNQ4 IN OHCS 60
3.3.2 LOSS OF GAA DOES NOT ALTER THE NUMBER
OF IHCS SYNAPTIC RIBBONS 61
3.3.3 LOSS OF GAU DIFFERENTIALLY DISTURBS THE ORIENTATION AND SHAPE OF
STEREOCILIA HAIR
BUNDLES IN OHCS
ALONG COCHLEAR TURNS 61
3.4 DELETION OF CAVL.2 IN CAVL.2
P
*
2
AND CAVL.2
EGR2
MOUSE COCHLEA 64
3.4.1 CAVL
.2 IS DELETED IN THE
COCHLEA AND BRAINSTEM NUCLEI IN CAVL
*2**
1
KO MICE 64
6
3.4.2 CAYL.2 IS DELETED IN SPECIFIC BRAINSTEM NUCLEI IN CAY
1.2^ ICO MICE 64
3.5 HEARING FUNCTION AND HAIR CELL PHENOTYPE
OF CAVL
.2 MOUSE LINES 63
3.5.1 HEARING SENSITIVITY OF THE TWO LINES
OF CAYL.2 MICE MUTANTS IS NORMAL 65
3.5.2 COCHLEAR AMPLIFICATION IN THE TWO LINES
OF CAVL
.2 MICE MUTANTS IS NORMAL 66
3.5.3 ABR WAVE AMPLITUDES
ARE AFFECTED IN CAVL.2
PN3
KO MICE 68
3.5.4 IHC SYNAPTIC RIBBONS ARE NOT
DISTURBED IN THE TWO CAYL.2 MICE MUTANTS 68
3.6 SUMMARY 70
4. DISCUSSION.................................
..................................................... 72
4.1 AUDITORY FUNCTION AND MOLECULAR PHENOTYPE OF GAJ ISOFOIMS AND MPINS
MICE MUTANTS.72
4.1.1 LACK OF GAU RESULTS IN REMARKABLY ALTERATION
OF AUDITORY FUNCTION 72
4.1.2 GAU PLAYS A MINOR ROLE IN MAINTAINING NORMAL AUDITORY FUNCTION 76
4.1.3 DEFICIENCY OF GOQ AND
GAU ISOFORMS OR MPINS RESULTS IN DEAFNESS 77
4.2 AUDITORY FUNCTION AND MOLECULAR
PHENOTYPES OF CAV
1.2 MICE MUTANTS 78
4.2.1 DELETION OF CAYL.2 DOES NOT ALTER HEARING SENSITIVITY AND
COCHLEAR AMPLIFICATION ...78
4.2.2 DIFFERENTIAL CONSEQUENCES OF THE DELETION OF CAYL.2 IN THE
PERIPHERAL OR CENTRAL
AUDITORY PATHWAY 79
4.3 SUMMARY 80
A^ERENCES...............................
................................
82
CONTRIBUTIONS.................................................
....................................... 94
CURRICULUM VITAE~. 95
LIST OF PUBLICATIONS...*...................
.......................................... 97
7
|
| any_adam_object | 1 |
| author | Lee, Sze Chim |
| author_GND | (DE-588)1070544779 |
| author_facet | Lee, Sze Chim |
| author_role | aut |
| author_sort | Lee, Sze Chim |
| author_variant | s c l sc scl |
| building | Verbundindex |
| bvnumber | BV042708233 |
| ctrlnum | (OCoLC)914356034 (DE-599)BSZ430212518 |
| dewey-full | 610 570 |
| dewey-hundreds | 600 - Technology (Applied sciences) 500 - Natural sciences and mathematics |
| dewey-ones | 610 - Medicine and health 570 - Biology |
| dewey-raw | 610 570 |
| dewey-search | 610 570 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health 570 - Biology |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| genre_facet | Hochschulschrift |
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| illustrated | Illustrated |
| indexdate | 2024-12-24T04:31:37Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-028139615 |
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| physical | 99, 12 S. Ill., graph. Darst. |
| publishDate | 2015 |
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| spellingShingle | Lee, Sze Chim Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants |
| subject_GND | (DE-588)4113937-9 |
| title | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants |
| title_auth | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants |
| title_exact_search | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants |
| title_full | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants vorgelegt von Sze Chim Lee |
| title_fullStr | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants vorgelegt von Sze Chim Lee |
| title_full_unstemmed | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants vorgelegt von Sze Chim Lee |
| title_short | Differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric G-protein and L-type voltage gated calcium channel Ca v 1.2 mice mutants |
| title_sort | differences in sound processing upon genetic mutations in epithelial or neuronal tissues by comparing heterotrimeric g protein and l type voltage gated calcium channel ca v 1 2 mice mutants |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028139615&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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