Inducible mouse model of chronic intestinal pseudo-obstruction by smooth muscle-specific inactivation of the SRF gene

Serum response factor (SRF) regulates the expression of muscle genes and immediate early genes. We investigated the consequences of inactivating this transcription factor SRF in adult gastrointestinal smooth muscle cells. SRF-floxed mice were crossed with SM-CreER(T2)(ki) mice expressing a tamoxifen...

Full description

Saved in:
Bibliographic Details
Published inGastroenterology (New York, N.Y. 1943) Vol. 133; no. 6; p. 1960
Main Authors Mericskay, Mathias, Blanc, Jocelyne, Tritsch, Eva, Moriez, Raphael, Aubert, Philippe, Neunlist, Michel, Feil, Robert, Li, Zhenlin
Format Journal Article
LanguageEnglish
Published United States 01.12.2007
Subjects
Online AccessGet more information

Cover

Loading…
Abstract Serum response factor (SRF) regulates the expression of muscle genes and immediate early genes. We investigated the consequences of inactivating this transcription factor SRF in adult gastrointestinal smooth muscle cells. SRF-floxed mice were crossed with SM-CreER(T2)(ki) mice expressing a tamoxifen-inducible recombinase in smooth muscle cells. Tamoxifen was injected into 12-week-old animals to activate the CreER(T2) and excise the SRF gene. SRF was down-regulated in the smooth muscle cells of the gastrointestinal tract, urinary bladder, and aorta. The mutant mice developed severe dilation of the intestinal tract associated with food stasis and air-fluid levels in the lumen 13 days after tamoxifen treatment. Mutant mice displayed cachexia and died between days 13 and 22. The dilation was associated with a thinning of the muscularis propria and was also observed in the urinary bladder. Ex vivo colonic contraction induced by electric field stimulation and carbachol was impaired in the mutant mice before the occurrence of the dilation phenotype. The expression of several genes, including those encoding smooth muscle actin, the heavy chain of smooth muscle myosin, and smoothelin, was 60% to 70% lower in mutants than in controls, and mutants also had a lower F/G actin ratio. SRF plays a central role in maintaining visceral smooth muscle contractile function in adults. Mice with a smooth muscle cell-specific SRF mutation develop a severe motility disorder resembling chronic intestinal pseudo-obstruction in humans and may be used as an inducible model of this disorder.
AbstractList Serum response factor (SRF) regulates the expression of muscle genes and immediate early genes. We investigated the consequences of inactivating this transcription factor SRF in adult gastrointestinal smooth muscle cells. SRF-floxed mice were crossed with SM-CreER(T2)(ki) mice expressing a tamoxifen-inducible recombinase in smooth muscle cells. Tamoxifen was injected into 12-week-old animals to activate the CreER(T2) and excise the SRF gene. SRF was down-regulated in the smooth muscle cells of the gastrointestinal tract, urinary bladder, and aorta. The mutant mice developed severe dilation of the intestinal tract associated with food stasis and air-fluid levels in the lumen 13 days after tamoxifen treatment. Mutant mice displayed cachexia and died between days 13 and 22. The dilation was associated with a thinning of the muscularis propria and was also observed in the urinary bladder. Ex vivo colonic contraction induced by electric field stimulation and carbachol was impaired in the mutant mice before the occurrence of the dilation phenotype. The expression of several genes, including those encoding smooth muscle actin, the heavy chain of smooth muscle myosin, and smoothelin, was 60% to 70% lower in mutants than in controls, and mutants also had a lower F/G actin ratio. SRF plays a central role in maintaining visceral smooth muscle contractile function in adults. Mice with a smooth muscle cell-specific SRF mutation develop a severe motility disorder resembling chronic intestinal pseudo-obstruction in humans and may be used as an inducible model of this disorder.
Author Mericskay, Mathias
Li, Zhenlin
Blanc, Jocelyne
Feil, Robert
Neunlist, Michel
Tritsch, Eva
Moriez, Raphael
Aubert, Philippe
Author_xml – sequence: 1
  givenname: Mathias
  surname: Mericskay
  fullname: Mericskay, Mathias
  email: merics@ccr.jussieu.fr
  organization: Pierre & Marie Curie University Paris 6, Paris, France; CNRS, UMR7079 Physiology and Physiopathology, Paris, France. merics@ccr.jussieu.fr
– sequence: 2
  givenname: Jocelyne
  surname: Blanc
  fullname: Blanc, Jocelyne
– sequence: 3
  givenname: Eva
  surname: Tritsch
  fullname: Tritsch, Eva
– sequence: 4
  givenname: Raphael
  surname: Moriez
  fullname: Moriez, Raphael
– sequence: 5
  givenname: Philippe
  surname: Aubert
  fullname: Aubert, Philippe
– sequence: 6
  givenname: Michel
  surname: Neunlist
  fullname: Neunlist, Michel
– sequence: 7
  givenname: Robert
  surname: Feil
  fullname: Feil, Robert
– sequence: 8
  givenname: Zhenlin
  surname: Li
  fullname: Li, Zhenlin
BackLink https://www.ncbi.nlm.nih.gov/pubmed/18054567$$D View this record in MEDLINE/PubMed
BookMark eNo1j9tKxDAYhIMo7kHfQCQv0PonTZv2UhZXFxYED9dLDn93u7RJaRph39666s3Mzcw3zIJcOu-QkDsGKYM8ezimexXGwaccQKZQpcDggsxZzssEgPEZWYRwBIAqK9k1mbEScpEXck7ixtloGt0i7XwMP2qxpb6m5jB41xjauBHD2DjV0j5gtD7xetqKZmy8o_pEQ-f9eKBdDKbFJPRomvrcU1PkS51jE288IH1_W9M9OrwhV7VqA97--ZJ8rp8-Vi_J9vV5s3rcJkYUbEyMZbIUhTSV1JgL1KbOoDJa1ILZDFXFIdOyKJFlwnJZgcq4qWWlUWBuC8aX5P6X20fdod31Q9Op4bT7_8-_AbRHYWk
CitedBy_id crossref_primary_10_1007_s00335_009_9245_y
crossref_primary_10_1186_s12915_016_0257_2
crossref_primary_10_1016_j_pupt_2012_06_006
crossref_primary_10_5056_jnm15183
crossref_primary_10_1152_ajpcell_00080_2010
crossref_primary_10_1007_s00535_018_1522_7
crossref_primary_10_1089_ten_teb_2014_0678
crossref_primary_10_1038_labinvest_2010_104
crossref_primary_10_1111_nmo_14357
crossref_primary_10_1371_journal_pone_0171262
crossref_primary_10_1016_j_ajpath_2022_07_013
crossref_primary_10_1152_ajpgi_00066_2021
crossref_primary_10_1016_j_devcel_2008_07_019
crossref_primary_10_1053_j_gastro_2016_12_017
crossref_primary_10_1038_s41598_021_91534_3
crossref_primary_10_1053_j_gastro_2010_06_041
crossref_primary_10_1038_s44161_022_00162_1
crossref_primary_10_1016_j_ajpath_2016_04_016
crossref_primary_10_1016_j_jcmgh_2020_09_014
crossref_primary_10_1053_j_gastro_2012_05_047
crossref_primary_10_1038_cddis_2015_353
crossref_primary_10_1053_j_gastro_2007_10_060
crossref_primary_10_1161_CIRCRESAHA_122_321109
crossref_primary_10_1053_j_gastro_2023_03_229
crossref_primary_10_1016_j_ymeth_2015_08_014
crossref_primary_10_1242_dev_029942
crossref_primary_10_1074_jbc_M113_478974
crossref_primary_10_1371_journal_pone_0115563
crossref_primary_10_1111_j_1365_2982_2008_01108_x
crossref_primary_10_1111_micc_12838
crossref_primary_10_1371_journal_pone_0018628
crossref_primary_10_3390_ijms241612597
crossref_primary_10_1016_j_ajpath_2023_09_013
crossref_primary_10_1111_nmo_13528
crossref_primary_10_1165_rcmb_2010_0316OC
crossref_primary_10_4103_2045_8932_93542
crossref_primary_10_1161_ATVBAHA_119_312449
crossref_primary_10_1371_journal_pone_0062292
crossref_primary_10_1053_j_sempedsurg_2009_07_001
crossref_primary_10_1161_ATVBAHA_122_318160
crossref_primary_10_3389_fphys_2021_710968
crossref_primary_10_1161_ATVBAHA_112_300708
crossref_primary_10_1016_j_bcp_2022_115307
crossref_primary_10_1161_CIRCRESAHA_113_301076
ContentType Journal Article
DBID CGR
CUY
CVF
ECM
EIF
NPM
DOI 10.1053/j.gastro.2007.09.010
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
DatabaseTitleList MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 1528-0012
ExternalDocumentID 18054567
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
--K
.1-
.55
.FO
.GJ
0R~
1B1
1CY
1P~
1~5
3O-
4.4
457
4G.
53G
5GY
5RE
5VS
7-5
AAEDT
AAEDW
AAIKJ
AALRI
AAQFI
AAQOH
AAQQT
AAQXK
AAXUO
AAYOK
ABCQX
ABJNI
ABLJU
ABMAC
ABOCM
ADBBV
ADMUD
ADPAM
AENEX
AEVXI
AFCTW
AFFNX
AFHKK
AFJKZ
AFRHN
AFTJW
AGHFR
AI.
AITUG
AJUYK
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
ASPBG
AVWKF
AZFZN
BELOY
BR6
C5W
CAG
CGR
COF
CS3
CUY
CVF
DU5
EBS
ECM
EFJIC
EIF
EJD
F5P
FD8
FDB
FEDTE
FGOYB
G8K
GBLVA
HVGLF
HZ~
IHE
J1W
J5H
K-O
KOM
L7B
M41
MO0
N4W
N9A
NPM
NQ-
O9-
OC.
OHT
ON0
P2P
PC.
QTD
R2-
RIG
ROL
RPZ
SEL
SES
SJN
SSZ
TWZ
UDS
UGJ
UV1
VH1
WH7
X7M
XH2
Y6R
YQJ
Z5R
ZGI
ZXP
ID FETCH-LOGICAL-c461t-cd178467c97be54ebcf309cb4f41d3ea9203b768e134d2790a32cf79be4e5d612
IngestDate Sat Sep 28 07:55:23 EDT 2024
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 6
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c461t-cd178467c97be54ebcf309cb4f41d3ea9203b768e134d2790a32cf79be4e5d612
OpenAccessLink http://www.gastrojournal.org/article/S0016508507016514/pdf
PMID 18054567
ParticipantIDs pubmed_primary_18054567
PublicationCentury 2000
PublicationDate 2007-12-01
PublicationDateYYYYMMDD 2007-12-01
PublicationDate_xml – month: 12
  year: 2007
  text: 2007-12-01
  day: 01
PublicationDecade 2000
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Gastroenterology (New York, N.Y. 1943)
PublicationTitleAlternate Gastroenterology
PublicationYear 2007
References 18054578 - Gastroenterology. 2007 Dec;133(6):2052-5
References_xml
SSID ssj0009381
Score 2.1557076
Snippet Serum response factor (SRF) regulates the expression of muscle genes and immediate early genes. We investigated the consequences of inactivating this...
SourceID pubmed
SourceType Index Database
StartPage 1960
SubjectTerms Actins - genetics
Animals
Cells, Cultured
Chronic Disease
Disease Models, Animal
Intestinal Pseudo-Obstruction - genetics
Mice
Mice, Inbred Strains
Muscle, Smooth - physiology
Serum Response Factor - genetics
Title Inducible mouse model of chronic intestinal pseudo-obstruction by smooth muscle-specific inactivation of the SRF gene
URI https://www.ncbi.nlm.nih.gov/pubmed/18054567
Volume 133
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELa6ICEuiDcsD_nAbZViJ05cHxFiWSF1D0tX2tvKdmwobJtqmx66v4yfx4ydpGkp4nGJojgaJZ4vo5nJzDeEvLG6YEZbnVgIvRIhtEtU7lliwRCqXEivPOYhx6fFybn4dJFfDAY_elVLq9oM7c3evpL_0SpcA71il-w_aLYTChfgHPQLR9AwHP9Kxzh3w06x9wkDeBfH2oRC8Uh5G8gg4Bueh3YrtyqrpDIdYyx6nstZBao6mq2WIDrBtkssHUIaDtvOPWurCD6fHeO85a3SoY8apFVI63kduZz2zPY54kr007lj_EW0_K7XsVWo_jrVm1T9FYAwJvWtu1pvfvlPrqf1Mk6tAt-_E1VBoB8y4Gd60VX_tzkM2asHcY3dRaJsxrcNc6TIaBDYN7NgNthe-8_CEI9vwy_h9RuGSjVkfOt20OJiFjDBRwxdSPnn1R1W7nbpgBzIEdrXU8wStWTP4Aa1bZp59nbf4yBZbSNiJ6AJjs3kPrnXRCT0XYTXAzJw84fkzripuXhEVh3KaEAZDSijlacNyugGZfRXlFGzphFldAdltI8ylAcoo4Ayiih7TM6PP0zenyTNsA74rAteJ7bkEn1Zq6RxuXDG-owpa4QXvMycVinLDMS2jmeiTKViOkutl8o44fIS_Own5Na8mrtnhEqRCssLZRVskGAjozj29Xk_ynSeFuY5eRo37HIRGVku2608_O3KC3J3A7yX5LYHE-BegT9Zm9dBeT8B8CB4XQ
link.rule.ids 783
linkProvider National Library of Medicine
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Inducible+mouse+model+of+chronic+intestinal+pseudo-obstruction+by+smooth+muscle-specific+inactivation+of+the+SRF+gene&rft.jtitle=Gastroenterology+%28New+York%2C+N.Y.+1943%29&rft.au=Mericskay%2C+Mathias&rft.au=Blanc%2C+Jocelyne&rft.au=Tritsch%2C+Eva&rft.au=Moriez%2C+Raphael&rft.date=2007-12-01&rft.eissn=1528-0012&rft.volume=133&rft.issue=6&rft.spage=1960&rft_id=info:doi/10.1053%2Fj.gastro.2007.09.010&rft_id=info%3Apmid%2F18054567&rft_id=info%3Apmid%2F18054567&rft.externalDocID=18054567