Sox7 and Sox17 are strain-specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice
| Autor: | Elisabetta Dejana, Dagmar Wilhelm, Fabrizio Orsenigo, Mathias Francois, Brett M. Hosking, Andrea Caprini, Catherine M. Browne, Peter Koopman, D. Tutt, Tara-Lynne Davidson, Terje Svingen |
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| Rok vydání: | 2009 |
| Předmět: |
Mice
Transgenic Biology Hypotrichosis Mice Species Specificity Downregulation and upregulation In vivo HMGB Proteins SOXF Transcription Factors medicine Animals Humans Lymphedema RNA Messenger Telangiectasis Lymphangiogenesis Molecular Biology Gene DNA Primers Homeodomain Proteins Mice Knockout Genetics Base Sequence Tumor Suppressor Proteins Gene Expression Regulation Developmental Syndrome Phenotype In vitro Up-Regulation Lymphatic system Mechanism of action Mice Inbred CBA medicine.symptom Function (biology) Developmental Biology |
| Zdroj: | Development. 136:2385-2391 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.034827 |
| Popis: | Developmental defects caused by targeted gene inactivation in mice are commonly subject to strain-specific modifiers that modulate the severity of the phenotype. Although several genetic modifier loci have been mapped in mice, the gene(s) residing at these loci are mostly unidentified, and the molecular mechanisms of modifier action remain poorly understood. Mutations in Sox18 cause a variable phenotype in the human congenital syndrome hypotrichosis-lymphedema-telangiectasia, and the phenotype of Sox18-null mice varies from essentially normal to completely devoid of lymphatic vasculature and lethal, depending on the strain of the mice,suggesting a crucial role for strain-specific modifiers in this system. Here we show that two closely related Group F Sox factors, SOX7 and SOX17, are able to functionally substitute for SOX18 in vitro and in vivo. SOX7 and SOX17 are not normally expressed during lymphatic development, excluding a conventional redundancy mechanism. Instead, these genes are activated specifically in the absence of SOX18 function, and only in certain strains. Our studies identify Sox7 and Sox17 as modifiers of the Sox18 mutant phenotype, and reveal their mechanism of action as a novel mode of strain-specific compensatory upregulation. |
| Databáze: | OpenAIRE |
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