title: A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development.
abstract: R-spondins are secreted ligands that bind cell surface receptors and activate Wnt/β-catenin signaling. Human mutations and gene inactivation studies in mice have revealed a role for these four proteins (RSPO1-4) in diverse developmental processes ranging from sex determination to limb development. Among the genes coding for R-spondins, only inactivation of Rspo3 shows early embryonic lethality (E10.5 in mice). Therefore, a conditional allele of this gene is necessary to understand the function of R-spondins throughout murine development. To address this need, we have produced an allele in which loxP sites flank exons 2-4 of Rspo3, allowing tissue-specific deletion of these exons in the presence of Cre recombinase. We used these mice to investigate the role of Rspo3 during limb development and found that limbs ultimately developed normally in the absence of Rspo3 function. However, severe hindlimb truncations resulted when Rspo3 and Rspo2 mutations were combined, demonstrating redundant function of these genes.
authors.affiliation: Department of Biological Sciences, 2500 University Drive N.W., University of Calgary, Calgary, Canada.
authors.forename: Stanley
authors.initials: S
authors.lastname: Neufeld
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosin
authors.forename: Anshula
authors.initials: A
authors.lastname: Ambasta
authors.forename: Kristen
authors.initials: K
authors.lastname: Hui
authors.forename: Venessa
authors.initials: V
authors.lastname: Shaneman
authors.forename: Ray
authors.initials: R
authors.lastname: Crowder
authors.forename: Lori
authors.initials: L
authors.lastname: Vickerman
authors.forename: John
authors.initials: J
authors.lastname: Cobb
mesh_terms: D000483:Alleles; D000818:Animals; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D017880:Limb Deformities, Congenital / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019699:Thrombospondins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000098907:R-Spondins
chemical_list: D019699:Thrombospondins; C517523:R-spondin3 protein, mouse; C518904:RSPO2 protein, mouse; D000098907:R-Spondins