排序方式: 共有66条查询结果,搜索用时 46 毫秒
61.
Zenz R Eferl R Kenner L Florin L Hummerich L Mehic D Scheuch H Angel P Tschachler E Wagner EF 《Nature》2005,437(7057):369-375
Psoriasis is a frequent, inflammatory disease of skin and joints with considerable morbidity. Here we report that in psoriatic lesions, epidermal keratinocytes have decreased expression of JunB, a gene localized in the psoriasis susceptibility region PSORS6. Likewise, inducible epidermal deletion of JunB and its functional companion c-Jun in adult mice leads (within two weeks) to a phenotype resembling the histological and molecular hallmarks of psoriasis, including arthritic lesions. In contrast to the skin phenotype, the development of arthritic lesions requires T and B cells and signalling through tumour necrosis factor receptor 1 (TNFR1). Prior to the disease onset, two chemotactic proteins (S100A8 and S100A9) previously mapped to the psoriasis susceptibility region PSORS4, are strongly induced in mutant keratinocytes in vivo and in vitro. We propose that the abrogation of JunB/activator protein 1 (AP-1) in keratinocytes triggers chemokine/cytokine expression, which recruits neutrophils and macrophages to the epidermis thereby contributing to the phenotypic changes observed in psoriasis. Thus, these data support the hypothesis that epidermal alterations are sufficient to initiate both skin lesions and arthritis in psoriasis. 相似文献
62.
Amnionless,essential for mouse gastrulation,is mutated in recessive hereditary megaloblastic anemia 总被引:7,自引:0,他引:7
Tanner SM Aminoff M Wright FA Liyanarachchi S Kuronen M Saarinen A Massika O Mandel H Broch H de la Chapelle A 《Nature genetics》2003,33(3):426-429
The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation. Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion. The embryos are severely compromised, surviving to the tenth day of gestation but seem to lack the mesodermal layers that normally produce the trunk. The Amn protein has one transmembrane domain separating a larger, N-terminal extracellular region and a smaller, C-terminal cytoplasmic region. The extracellular region harbors a cysteine-rich domain resembling those occurring in Chordin, found in Xenopus laevis embryos, and Sog, found in Drosophila melanogaster. As these cysteine-rich domains bind bone morphogenetic proteins (Bmps), it has been speculated that the cysteine-rich domain in Amn also binds Bmps. We show that homozygous mutations affecting exons 1-4 of human AMN lead to selective malabsorption of vitamin B12 (a phenotype associated with megaloblastic anemia 1, MGA1; OMIM 261100; refs. 5,6) in otherwise normal individuals, suggesting that the 5' end of AMN is dispensable for embryonic development but necessary for absorption of vitamin B12. When the 5' end of AMN is truncated by mutations, translation is initiated from alternative downstream start codons. 相似文献
63.
标准载荷累积频次谱的引入给构件疲劳寿命预测方法的研究和应用带来了方便。但是,对于这种累积频次谱的外推却没有相应的简便方法。为解决这一问题,本文提出了仅以计算分析为基础的标准载荷累积频次谱的外推方法。文中所导公式适用于各种起讫范围的外推计算。通过与以往的方法相比较,所得外推结果令人满意。 相似文献
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Sarparanta J Jonson PH Golzio C Sandell S Luque H Screen M McDonald K Stajich JM Mahjneh I Vihola A Raheem O Penttilä S Lehtinen S Huovinen S Palmio J Tasca G Ricci E Hackman P Hauser M Katsanis N Udd B 《Nature genetics》2012,44(4):450-5, S1-2
Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36 over a decade ago, but its genetic cause has remained elusive. Here we studied nine LGMD-affected families from Finland, the United States and Italy and identified four dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile changes in the ubiquitously expressed co-chaperone DNAJB6. Functional testing in vivo showed that the mutations have a dominant toxic effect mediated specifically by the cytoplasmic isoform of DNAJB6. In vitro studies demonstrated that the mutations increase the half-life of DNAJB6, extending this effect to the wild-type protein, and reduce its protective anti-aggregation effect. Further, we show that DNAJB6 interacts with members of the CASA complex, including the myofibrillar myopathy-causing protein BAG3. Our data identify the genetic cause of LGMD1D, suggest that its pathogenesis is mediated by defective chaperone function and highlight how mutations in a ubiquitously expressed gene can exert effects in a tissue-, isoform- and cellular compartment-specific manner. 相似文献
66.
Albers CA Paul DS Schulze H Freson K Stephens JC Smethurst PA Jolley JD Cvejic A Kostadima M Bertone P Breuning MH Debili N Deloukas P Favier R Fiedler J Hobbs CM Huang N Hurles ME Kiddle G Krapels I Nurden P Ruivenkamp CA Sambrook JG Smith K Stemple DL Strauss G Thys C van Geet C Newbury-Ecob R Ouwehand WH Ghevaert C 《Nature genetics》2012,44(4):435-9, S1-2