排序方式: 共有11条查询结果,搜索用时 556 毫秒
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Garcia-Gonzalo FR Corbit KC Sirerol-Piquer MS Ramaswami G Otto EA Noriega TR Seol AD Robinson JF Bennett CL Josifova DJ García-Verdugo JM Katsanis N Hildebrandt F Reiter JF 《Nature genetics》2011,43(8):776-784
Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies. 相似文献
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Davis EE Zhang Q Liu Q Diplas BH Davey LM Hartley J Stoetzel C Szymanska K Ramaswami G Logan CV Muzny DM Young AC Wheeler DA Cruz P Morgan M Lewis LR Cherukuri P Maskeri B Hansen NF Mullikin JC Blakesley RW Bouffard GG;NISC Comparative Sequencing Program Gyapay G Rieger S Tönshoff B Kern I Soliman NA Neuhaus TJ Swoboda KJ Kayserili H Gallagher TE Lewis RA Bergmann C Otto EA Saunier S Scambler PJ Beales PL Gleeson JG Maher ER Attié-Bitach T Dollfus H Johnson CA Green ED Gibbs RA Hildebrandt F 《Nature genetics》2011,43(3):189-196
Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ~5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. 相似文献
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Zusammenfassung Mit der Gömöri-Technik wurden beiArtemia drei Typen neurosektretorischer Zellen nachgewiesen. Im Gehirn sind grosse, ovale Zellen mit vakuolisiertem Cytoplasma vorhanden, von denen einige grosse Axone besitzen. Der 2. Typus ist kleiner und weist keine zum Augenstiel führenden Fortsätze auf. Der 3. Typus liegt als traubenförmige Gruppen von Zellen im X-Organ des Augenstiels. Wahrscheinlich ist ventral am Gehirn ein Depotorgan für das Sekret des 1. Typus vorhanden. Die Beziehung dieser Zellen zur parthenogenetischen Vermehrung der Art wird untersucht. 相似文献
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Zusammenfassung Ungleichgeschlechtige Zwillinge von verschiedener Grösse vonMegaderma lyra lyra (Microchiroptera) wurden im April letzten Jahres in einem trächtigen Weibchen gefunden. Um die Grössendifferenz der Zwillinge zu erklären, wird angenommen, dass in diesem Falle zwei Eier befruchtet worden waren, dass die linke Zygote einen Vorsprung über die rechte gewann und dass deshalb dic Implantation der rechten Blastocyste verzögert wurde. 相似文献
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W Zhou EA Otto A Cluckey R Airik TW Hurd M Chaki K Diaz FP Lach GR Bennett HY Gee AK Ghosh S Natarajan S Thongthip U Veturi SJ Allen S Janssen G Ramaswami J Dixon F Burkhalter M Spoendlin H Moch MJ Mihatsch J Verine R Reade H Soliman M Godin D Kiss G Monga G Mazzucco K Amann F Artunc RC Newland T Wiech S Zschiedrich TB Huber A Friedl GG Slaats JA Joles R Goldschmeding J Washburn RH Giles S Levy A Smogorzewska F Hildebrandt 《Nature genetics》2012,44(8):910-915
Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD. 相似文献
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Zusammenfassung Da Kadmium schwere Schädigungen im Hoden hervorrufen kann, wurde die Adenohypophyse bei 14 männlichenPresbytis entellus entellus nach testikulärer Nekrose untersucht. Die verschiedenen Zellen der Adenohypophyse zeigen unterschiedliche Reaktionen, zum Teil mit Vakuolen und Granulationen. Nach Ablauf eines Jahres wird eine Erholung solcher Zellen beobachtet mit gleichzeitiger Regeneration des Hodenepithels und der Zwischenzellen.
This work was supported by a grant from the Ford Foundation. 相似文献
This work was supported by a grant from the Ford Foundation. 相似文献