The addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins (referred to as O-GlcNAcylation) is a modification that is crucial for vertebrate development. O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). Missense variants of OGT have recently been shown to segregate with an X-linked syndromic form of intellectual disability, OGT-linked congenital disorder of glycosylation (OGT-CDG). Although the existence of OGT-CDG suggests that O-GlcNAcylation is crucial for neurodevelopment and/or cognitive function, the underlying pathophysiologic mechanisms remain unknown. Here we report a mouse line that carries a catalytically impaired OGT-CDG variant. These mice show altered O-GlcNAc homeostasis with decreased global O-GlcNAcylation and reduced levels of OGT and OGA in the brain. Phenotypic characterization of the mice revealed lower body weight associated with reduced body fat mass, short stature and microcephaly. This mouse model will serve as an important tool to study genotype-phenotype correlations in OGT-CDG in vivo and for the development of possible treatment avenues for this disorder.

• Klíčová slova
• O-GlcNAcylation, Intellectual disability, Vertebrate development,
• MeSH
• beta-N-acetylhexosaminidasy metabolismus   MeSH
• fenotyp MeSH
• glykosylace MeSH
• mentální retardace * genetika   MeSH
• modely nemocí na zvířatech * MeSH
• mozek patologie   metabolismus   MeSH
• myši MeSH
• N-acetylglukosaminyltransferasy * metabolismus   genetika   nedostatek   MeSH
• neurovývojové poruchy patologie   genetika   enzymologie   MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• beta-N-acetylhexosaminidasy MeSH
• hexosaminidase C MeSH Prohlížeč
• N-acetylglukosaminyltransferasy * MeSH
• O-GlcNAc transferase MeSH Prohlížeč

Hereditary multiple exostoses (HME) represents a heterogeneous group of diseases often associated with progressive skeletal deformities. Most frequently, mutations in EXT1 and EXT2 genes with autosomal dominant inheritance are responsible for HME. In our group of 9 families with HME we evaluated the clinical course of the disease and analysed molecular background using Sanger sequencing and MLPA in EXT1 and EXT2 genes. The mean age in our group of patients, when the first exostosis was recognised was 4.5 years (range 2-10 years) and the number of exostoses per one patient documented on X-ray ranged from 2 to 54. Most of the exostoses developed before the growth was completed and they were dominantly localised in the distal femurs, proximal tibia, proximal humerus and distal radius. In all patients, at least one to 8 surgeries were necessary due to complaints and local complications, but neither patient developed malignant transformation. In half of the patients, the disease resulted in short stature. DNA analyses were positive in 7 families. In five probands, different EXT1 gene mutations resulting in premature stop-codon (p.Gly124Argfs*65, p.Leu191*, p.Trp364Lysfs*11, p.Val371Glyfs*10, p.Leu490Profs*31) were found. In two probands, nonsense mutations were found in EXT2 gene (p.Val187Profs*115, p.Cys319fs*46). Five mutations have been novel and two mutations have occurred de novo in probands. Although the risk for malignant transformation is usually low, especially in patients with low number of exostoses, early diagnostics and longitudinal follow up of patients is of a big importance, because early surgery can prevent progression of secondary bone deformities.

• Klíčová slova
• EXT1, EXT2, Multiple exostoses,
• MeSH
• dědičné mnohočetné exostózy diagnostické zobrazování   genetika   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• N-acetylglukosaminyltransferasy genetika   MeSH
• předškolní dítě MeSH
• sekvenční analýza DNA MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• Exostosin 1 MeSH
• Exostosin 2 MeSH
• N-acetylglukosaminyltransferasy MeSH

We investigated the role of natural killer (NK) cells and CD161, their primary C-type-lectin-like receptor in rheumatoid arthritis (RA). Samples were compared with healthy donors (HD), dermatomyositic (DM), polymyositic (PM), and osteoarthritic (OA) patients. RA, PM, and DM NK cell cytotoxicities significantly decreased relative to the HD and OA NK cells (p<0.0001). These results correlated with an increased expression of NK cell inhibitory receptor CD161, in active disease RA patients. We demonstrated that NK cells are able to respond to mutated citrullinated vimentin (MCV), an RA-specific autoantigen, leading to increases in both PAD4 enzyme and CD161 mRNA expression. MGAT5 glycosidase involvement was detected in GlcNAc metabolism within the synoviocytes of RA patients. Our findings reveal a functional relationship between CD161 expression and NK cell cytotoxicity as well as reactivity to glycans and MCV, thus providing new insight into the pathogenesis of RA and confirming the involvement of surface glycosylation.

• MeSH
• autoantigeny farmakologie   MeSH
• autoimunitní nemoci imunologie   MeSH
• autoprotilátky krev   imunologie   MeSH
• buňky NK cytologie   účinky léků   imunologie   metabolismus   MeSH
• cytotoxicita imunologická účinky léků   imunologie   MeSH
• dermatomyozitida imunologie   MeSH
• dospělí MeSH
• exprese genu účinky léků   genetika   MeSH
• glukokortikoidy terapeutické užití   MeSH
• glykokonjugáty farmakologie   MeSH
• hydrolasy genetika   MeSH
• imunosupresiva terapeutické užití   MeSH
• lektinové receptory NK-buněk - podrodina B agonisté   genetika   metabolismus   MeSH
• leukocyty mononukleární cytologie   účinky léků   imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• N-acetylglukosaminyltransferasy genetika   MeSH
• osteoartróza imunologie   MeSH
• peptidylarginindeiminasa typu 4 MeSH
• peptidylarginindeiminasy MeSH
• počet buněk MeSH
• polymyozitida imunologie   MeSH
• polysacharidy farmakologie   MeSH
• revmatoidní artritida diagnóza   farmakoterapie   imunologie   MeSH
• senioři MeSH
• synoviální tekutina cytologie   metabolismus   MeSH
• vimentin farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase MeSH Prohlížeč
• autoantigeny MeSH
• autoprotilátky MeSH
• glukokortikoidy MeSH
• glykokonjugáty MeSH
• hydrolasy MeSH
• imunosupresiva MeSH
• lektinové receptory NK-buněk - podrodina B MeSH
• N-acetylglukosaminyltransferasy MeSH
• PADI4 protein, human MeSH Prohlížeč
• peptidylarginindeiminasa typu 4 MeSH
• peptidylarginindeiminasy MeSH
• polysacharidy MeSH
• vimentin MeSH

• MeSH
• mapování chromozomů veterinární   MeSH
• molekulární sekvence - údaje MeSH
• N-acetylglukosaminyltransferasy genetika   MeSH
• polymorfismus délky restrikčních fragmentů * MeSH
• prasata genetika   MeSH
• restrikční endonukleasy typu II MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Exostosin 1 MeSH
• GGCC-specific type II deoxyribonucleases MeSH Prohlížeč
• N-acetylglukosaminyltransferasy MeSH
• restrikční endonukleasy typu II MeSH

A 4.5-kb BamHI fragment of chromosomal DNA of Streptomyces collinus containing gene ftsZ was cloned and sequenced. Upstream of ftsZ are localized genes ftsQ, murG, and ftsW, and downstream is yfiH. Gene ftsA is not adjacent to ftsZ or other genes of the cloned fragment. Protein FtsZ was isolated and characterized with respect to its binding to GTP and GTPase activity. The binding of GTP to FtsZ was Ca(2+) or Mg(2+) dependent with an optimum at 10 mM. The rate of GTP hydrolysis by FtsZ was stimulated by KCl. The presence of Ca(2+) (3-5 mM) resulted in a significant increase of GTPase activity. Higher concentrations of Ca(2+) than 5 mM had an inhibitory effect on GTPase activity. These results indicate that divalent ions (Ca(2+) or Mg(2+)) can be involved in regulation of GTP binding and hydrolysis of FtsZ. The maximum level of FtsZ was detected in aerial mycelium when spiral loops and sporulation septa were formed. FtsZ is degraded after finishing sporulation septa.

• MeSH
• antibakteriální látky metabolismus   MeSH
• bakteriální geny * MeSH
• bakteriální proteiny chemie   genetika   MeSH
• buněčný cyklus genetika   MeSH
• cytoskeletální proteiny * MeSH
• DNA bakterií analýza   MeSH
• GTP-fosfohydrolasy metabolismus   MeSH
• guanosintrifosfát metabolismus   MeSH
• membránové proteiny chemie   genetika   MeSH
• multigenová rodina * MeSH
• N-acetylglukosaminyltransferasy chemie   genetika   MeSH
• proteiny vnější bakteriální membrány * MeSH
• proteiny z Escherichia coli * MeSH
• pyridony metabolismus   MeSH
• sekvenční analýza MeSH
• Streptomyces genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• bakteriální proteiny MeSH
• cytoskeletální proteiny * MeSH
• DNA bakterií MeSH
• FtsQ protein, E coli MeSH Prohlížeč
• FtsW protein, Bacteria MeSH Prohlížeč
• FtsZ protein, Bacteria MeSH Prohlížeč
• GTP-fosfohydrolasy MeSH
• guanosintrifosfát MeSH
• membránové proteiny MeSH
• mocimycin MeSH Prohlížeč
• N-acetylglukosaminyltransferasy MeSH
• proteiny vnější bakteriální membrány * MeSH
• proteiny z Escherichia coli * MeSH
• pyridony MeSH
• UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase MeSH Prohlížeč