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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 01, 2008 |
| Title |
Effect of BMPR2-R899X mutation in lung with and without elevated RVSP |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Familial pulmonary arterial hypertension (fPAH) is associated with mutations in BMPR2. Many of these mutations occur in the BMPR2 tail domain, leaving the SMAD functions intact. In order to determine the in vivo consequences of BMPR2 tail domain mutation, we created a smooth-muscle specific doxycycline inducible BMPR2 mutation with an arginine to termination mutation at amino acid 899. When these SM22-rtTA x TetO7-BMPR2R899X mice had transgene induced for 9 weeks, starting at 4 weeks of age, they universally developed pulmonary vascular pruning as assessed by fluorescent microangiography. Approximately half the time the induced animals developed elevated right ventricular systolic pressures (RVSP), associated with extensive pruning, muscularization of small pulmonary vessels, and development of large structural pulmonary vascular changes. These lesions included large numbers of macrophages and T-cells in their adventitial compartment, as well as CD133 positive cells in the lumen. Small vessels filled with CD45 positive and sometimes CD3 positive cells were a common feature in all SM22-rtTA x TetO7-BMPR2R899X mice. Gene array experiments show changes in stress response, muscle organization and function, proliferation and apoptosis, and developmental pathways before RVSP increases. Our results show that the primary phenotypic result of BMPR2 tail domain mutation in smooth muscle is pulmonary vascular pruning leading to elevated RVSP, associated with early dysregulation in multiple pathways with clear relevance to PAH. This model should be useful to the research community in examining early molecular and physical events in the development of PAH, and as a platform to validate potential treatments.
Keywords: Disease state analysis
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| Overall design |
Each array is an individual female mouse, age-matched, with two mice & arrays used for each of controls (transactivator only), BMPR2-R899X with normal RVSP, and BMPR2-R899X with high RVSP.
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| Contributor(s) |
West J, Harral J, Lane K, Deng Y, Ickes B, Albu S, Crona D, Stewart D, Fagan K |
| Citation(s) |
18723761 |
| Submission date |
Apr 01, 2008 |
| Last update date |
Feb 11, 2019 |
| Contact name |
James West |
| E-mail(s) |
j.west@vanderbilt.edu
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| Organization name |
Vanderbilt University
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| Department |
Medicine
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| Lab |
Pulmonary
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| Street address |
4200 E 9TH Ave, Box B133
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| City |
Nashville |
| State/province |
TN |
| ZIP/Postal code |
37201 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| GSM278697 |
Control SM22-rtTA +9 weeks dox - mouse 4443 |
| GSM278698 |
Control SM22-rtTA +9 weeks dox - mouse 4446 |
| GSM278699 |
SM22-BMPR2-R899X with 9 weeks doxycycline and normal RVSP - 4518 |
| GSM278700 |
SM22-BMPR2-R899X with 9 weeks doxycycline and normal RVSP - 4445 |
| GSM278701 |
SM22-BMPR2-R899X with 9 weeks doxycycline and high RVSP - 4453 |
| GSM278702 |
SM22-BMPR2-R899X with 9 weeks doxycycline and high RVSP - 4444 |
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| Relations |
| BioProject |
PRJNA107111 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11018_RAW.tar |
23.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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