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Mutations of the GREAT gene cause cryptorchidism 总被引:7,自引:0,他引:7
Gorlov IP Kamat A Bogatcheva NV Jones E Lamb DJ Truong A Bishop CE McElreavey K Agoulnik AI 《Human molecular genetics》2002,11(19):2309-2318
In humans, failure of testicular descent (cryptorchidism) is one of the most frequent congenital malformations, affecting 1-3% of newborn boys. The clinical consequences of this abnormality are infertility in adulthood and a significantly increased risk of testicular malignancy. Recently, we described a mouse transgene insertional mutation, crsp, causing high intraabdominal cryptorchidism in homozygous males. A candidate gene Great (G-protein-coupled receptor affecting testis descent), was identified within the transgene integration site. Great encodes a seven-transmembrane receptor with a close similarity to the glycoprotein hormone receptors. The Great gene is highly expressed in the gubernaculum, the ligament that controls testicular movement during development, and therefore may be responsible for mediating hormonal signals that affect testicular descent. Here we show that genetic targeting of the Great gene in mice causes infertile bilateral intraabdominal cryptorchidism. The mutant gubernaculae fail to differentiate, indicating that the Great gene controls their development. Mutation screening of the human GREAT gene was performed using DHPLC analysis of the genomic DNA from 60 cryptorchid patients. Nucleotide variations in GREAT cDNA were found in both the patient and the control populations. A unique missense mutation (T222P) in the ectodomain of the GREAT receptor was identified in one of the patients. This mutant receptor fails to respond to ligand stimulation, implicating the GREAT gene in the etiology in some cases of cryptorchidism in humans. 相似文献
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Desantis S Corriero A Acone F Zubani D Cirillo F Palmieri G De Metrio G 《Acta histochemica》2003,105(1):73-79
Expression of sugar residues and the nature of oligosaccharide linkage during keratinocyte maturation in the epidermis of the Breton dog were studied with the use of lectin histochemistry. Thirteen lectins were used. Labelling was not observed with GSA I-B4, GSA II, UEA-I, and LTA. The cytoplasm of keratinocytes reacted with PNA, HPA, Con A, and WGA from the basal layer to the granular layer. PNA and Con A showed highest reactivity in the granular cell layer. The cell surface showed increased reactivity with PNA, HPA, and WGA with maturation of keratinocytes. KOH-neuraminidase treatment (KOH-Neu) increased PNA and RCA120 staining during keratinocyte differentiation thus indicating an increase in oligosaccharides terminating with sialic acid-Galbeta(1,3)GalNAc and sialic acid-Galbeta(1,4)GlcNAc, respectively. Labelling of the glycocalyx of basal and spinous keratinocytes with SNA and MAA revealed terminal Neu5acalpha(2,6)Gal/GalNAc and Neu5acalpha(2,3)Galbeta(1,4)GlcNAc. KOH-Neu-DBA showed oligosaccharides terminating with sialic acid-GalNAcalpha(1,3)GalNAc in the spinous and granular layers. A selective glycocalyx labelling of granular keratinocytes was observed with DBA and SBA. Reactions with MAA, PNA, DBA, RCA120, SBA, HPA, and WGA disappeared after the beta-elimination reaction. Our findings indicate that Breton dog epidermis contains more O-linked than N-linked oligosaccharides and confirm that different subpopulations of keratinocytes can be distinguished by lectin histochemistry. 相似文献
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During the past 10 years knowledge about the interactions between major histocompatibility complex (MHC) class I molecules
and the T-cell receptor (TCR) complex of cytotoxic T-cells (CTL) has developed dramatically. But the primary interest, both
with respect to structure as well as function, has concentrated on HLA-A and -B molecules because of their high sequence polymorphism
and their dominating presence at the cell surface. In contrast, HLA-C molecules seemed to be of only minor importance in the
cascade of immune reactions owing to their more limited polymorphism and reduced levels of surface expression. The inability
to define a number of antigen specificities had the result that HLA-C molecules were often neglected in studies of immune
response, transplantation, and disease association. More recently a new function has been identified for HLA class I molecules
where they act as inhibitors of the lytic capacity of natural killer (NK) cells and non-MHC-restricted T-cells. Moreover,
the understanding of this novel mode of negative regulation of cytotoxicity was remarkably influenced by HLA-C since these
were the first HLA class I molecules found to have such inhibitory potential. With this new inhibitory function serving as
an essential component of the immune system, HLA-C molecules can no longer be neglected. 相似文献
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Marqué S Poirel L Héritier C Brisse S Blasco MD Filip R Coman G Naas T Nordmann P 《Journal of clinical microbiology》2005,43(9):4885-4888
The spread of the plasmid-mediated carbapenem-hydrolyzing oxacillinase OXA-58 was detected in Acinetobacter sp. clinical isolates from southern Europe, the Balkans, and central Turkey. It may contribute significantly to the emergence of carbapenem resistance in Acinetobacter spp., at least in this part of the world. 相似文献
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