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Series GSE61728 Query DataSets for GSE61728
Status Public on Sep 24, 2015
Title The Tsk2/+ mouse fibrotic phenotype is due to a gain-of-function mutation in the PIIINP segment of the Col3a1 gene
Organism Mus musculus
Experiment type Expression profiling by array
Summary Systemic sclerosis (SSc) is a polygenic, autoimmune disorder of unknown etiology, characterized by the excessive accumulation of extracellular matrix (ECM) proteins, vascular alterations, and autoantibodies. The tight skin (Tsk)2/+ mouse model of SSc demonstrates signs similar to SSc including tight skin and excessive deposition of dermal ECM proteins. By linkage analysis, we mapped the Tsk2 gene mutation to less than 3 megabases on chromosome 1. We performed both RNA sequencing of skin transcripts and genome capture DNA sequencing of the region spanning this interval in Tsk2/+ and wild-type littermates. A missense point mutation in the procollagen III amino terminal propeptide segment (PIIINP) of Col3a1 was found to be the best candidate for Tsk2, so both in vivo and in vitro genetic complementation tests were used to prove that this Col3a1 mutation is the Tsk2 gene. All previously documented mutations in the human Col3a1 gene are associated with Ehlers-Danlos syndrome, a connective tissue disorder that leads to a defect in type III collagen synthesis. The Tsk2 point mutation is the first documented gain-of-function mutation associated with Col3a1, which leads instead to fibrosis. This discovery provides insight into the mechanism of skin fibrosis manifested by Tsk2/+ mice.
Overall design For the transfection experiment, three Col3a1 knockout fibroblast transfected with WT Col3a1 samples and three Col3a1 knockout fibroblast transfected with Tsk2 Col3a1 samples were used. For the 4-week female, three WT mice and three Tsk2 total skin RNA were used.
Contributor(s) Long K, Li Z, Burgwin C
Citation(s) 25330296
Submission date Sep 24, 2014
Last update date Jan 12, 2017
Contact name Michael Whitfield
Phone 6036501105
Organization name Geisel School of Medicine at Dartmouth
Department Genetics
Street address 710 Remsen 74 College Street
City Hanover
State/province New Hampshire
ZIP/Postal code 03755
Country USA
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (14)
GSM1511881 Tsk2 TF1
GSM1511882 Tsk2 TF2
GSM1511883 Tsk2 TF3
BioProject PRJNA261965

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Supplementary file Size Download File type/resource
GSE61728_RAW.tar 83.7 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table

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