A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre
Frutkin, Andrew D. ; Shi, Haikun ; Otsuka, Goro ; Levéen, Per LU ; Karlsson, Stefan LU
and Dichek, David A.
(2006)
In Journal of Molecular and Cellular Cardiology
41(4).
p.724-731
- Abstract
- Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type 11 TGF-beta receptor (tgfbr2(flox)) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2(flox). Surprisingly, SMMHC-Cre rnice recombined tglbr2(flox) at low levels in SMC and at high levels in the testis. Recombination of tgfbr2(flox) in testis correlated with high-level... (More)
- Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type 11 TGF-beta receptor (tgfbr2(flox)) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2(flox). Surprisingly, SMMHC-Cre rnice recombined tglbr2(flox) at low levels in SMC and at high levels in the testis. Recombination of tgfbr2(flox) in testis correlated with high-level expression of SMMHC-Cre in testis and germline transmission of tgfbr2(null). In contrast, mice expressing Cre from a SM22 alpha promoter (SM22-Cre) efficiently recombined tgfbr2(flox) in vascular and visceral SMC and the heart, but not in testis. Use of the R26R reporter allele confirmed that Cre-mediated recombination in vascular SMC was inefficient for SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced the SM22-Cre allele into tgfbr2(flox) zygotes in order to generate adult mice that are hemizygous for SM22-Cre and homozygous for tgfbr2(flox) and would have conversion of tgfbr2(flox/flox) to tgfbr2(null/null) in SMC-produced no live SM22-Cre : tgfbr2(flox/flox) pups (P < 0.001). We conclude: (1) "SMC-targeted" Cre lines vary significantly in specificity and efficiency of Cre expression; (2) TGF-beta signaling in the subset of cells that express SM22 alpha is required for normal development; (3) generation of adult mice with absent TGF-beta signaling in SMC remains a challenge. (c) 2006 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/386704
- author
- Frutkin, Andrew D.
; Shi, Haikun
; Otsuka, Goro
; Levéen, Per
LU
; Karlsson, Stefan
LU
and Dichek, David A.
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- SM22 alpha, smooth, Cre recombinase, smooth muscle cells, type II TGF-beta receptor, muscle myosin heavy chain
- in
- Journal of Molecular and Cellular Cardiology
- volume
- 41
- issue
- 4
- pages
- 724 - 731
- publisher
- Elsevier
- external identifiers
-
- wos:000241403900018
- scopus:33748542875
- pmid:16887142
- ISSN
- 1095-8584
- DOI
- 10.1016/j.yjmcc.2006.06.067
- language
- English
- LU publication?
- yes
- id
- e169c8e8-31c9-493a-b0df-4609e8680d30 (old id 386704)
- date added to LUP
- 2016-04-01 16:06:34
- date last changed
- 2022-02-12 19:48:09
@article{e169c8e8-31c9-493a-b0df-4609e8680d30,
abstract = {{Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type 11 TGF-beta receptor (tgfbr2(flox)) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2(flox). Surprisingly, SMMHC-Cre rnice recombined tglbr2(flox) at low levels in SMC and at high levels in the testis. Recombination of tgfbr2(flox) in testis correlated with high-level expression of SMMHC-Cre in testis and germline transmission of tgfbr2(null). In contrast, mice expressing Cre from a SM22 alpha promoter (SM22-Cre) efficiently recombined tgfbr2(flox) in vascular and visceral SMC and the heart, but not in testis. Use of the R26R reporter allele confirmed that Cre-mediated recombination in vascular SMC was inefficient for SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced the SM22-Cre allele into tgfbr2(flox) zygotes in order to generate adult mice that are hemizygous for SM22-Cre and homozygous for tgfbr2(flox) and would have conversion of tgfbr2(flox/flox) to tgfbr2(null/null) in SMC-produced no live SM22-Cre : tgfbr2(flox/flox) pups (P < 0.001). We conclude: (1) "SMC-targeted" Cre lines vary significantly in specificity and efficiency of Cre expression; (2) TGF-beta signaling in the subset of cells that express SM22 alpha is required for normal development; (3) generation of adult mice with absent TGF-beta signaling in SMC remains a challenge. (c) 2006 Elsevier Inc. All rights reserved.}},
author = {{Frutkin, Andrew D. and Shi, Haikun and Otsuka, Goro and Levéen, Per and Karlsson, Stefan and Dichek, David A.}},
issn = {{1095-8584}},
keywords = {{SM22 alpha; smooth; Cre recombinase; smooth muscle cells; type II TGF-beta receptor; muscle myosin heavy chain}},
language = {{eng}},
number = {{4}},
pages = {{724--731}},
publisher = {{Elsevier}},
series = {{Journal of Molecular and Cellular Cardiology}},
title = {{A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre}},
url = {{http://dx.doi.org/10.1016/j.yjmcc.2006.06.067}},
doi = {{10.1016/j.yjmcc.2006.06.067}},
volume = {{41}},
year = {{2006}},
}