Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse
| Autor: | Yasayko Sa, Hjerrild Ka, John E. Wilkinson, Jeffery Ew, Fred Ramsdell, David J. Galas, Mary E. Brunkow, L B Clark, Steven F. Ziegler, Bryan W. Paeper |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
animal structures Amino Acid Motifs DNA Mutational Analysis Molecular Sequence Data Genes Recessive Mice Transgenic Biology Winged Helix medicine.disease_cause Conserved sequence Mice Forkhead Transcription Factors Protein structure Genetics medicine Animals Humans Amino Acid Sequence Lymphocyte Count RNA Messenger Cloning Molecular Gene Conserved Sequence Mutation Genes Essential Gene Expression Profiling Genetic Complementation Test IPEX syndrome Physical Chromosome Mapping medicine.disease Molecular biology Phenotype Lymphoproliferative Disorders Mice Mutant Strains Protein Structure Tertiary DNA-Binding Proteins Female Lymph Nodes Sequence Alignment |
| Zdroj: | Nature Genetics. 27:68-73 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/83784 |
| Popis: | Scurfy (sf) is an X-linked recessive mouse mutant resulting in lethality in hemizygous males 16-25 days after birth, and is characterized by overproliferation of CD4+CD8- T lymphocytes, extensive multiorgan infiltration and elevation of numerous cytokines. Similar to animals that lack expression of either Ctla-4 or Tgf-beta, the pathology observed in sf mice seems to result from an inability to properly regulate CD4+CD8- T-cell activity. Here we identify the gene defective in sf mice by combining high-resolution genetic and physical mapping with large-scale sequence analysis. The protein encoded by this gene (designated Foxp3) is a new member of the forkhead/winged-helix family of transcriptional regulators and is highly conserved in humans. In sf mice, a frameshift mutation results in a product lacking the forkhead domain. Genetic complementation demonstrates that the protein product of Foxp3, scurfin, is essential for normal immune homeostasis. |
| Databáze: | OpenAIRE |
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