Nevo N.,French Institute of Health and Medical Research |
Nevo N.,University of Paris Descartes |
Chol M.,French Institute of Health and Medical Research |
Chol M.,University of Paris Descartes |
And 11 more authors.
Nephrology Dialysis Transplantation | Year: 2010
Background. Cystinosis is caused by mutations in CTNS that encodes cystinosin, the lysosomal cystine transporter. The most severe and frequent form is characterized by a proximal tubulopathy that appears around 6 to 12 months of age. In the absence of treatment, end-stage renal disease is reached by 10 years. Ctns -/- mice of a mixed 129Sv × C57BL/6 genetic background show elevated renal cystine levels; however, proximal tubulopathy or end-stage renal disease is not observed. Methods. As renal phenotype can be influenced by genetic background, we generated congenic C57BL/6 and FVB/N Ctns -/- mice and assayed renal lesions and function by histological and biochemical studies. Results. C57BL/6 Ctns -/- mice showed significantly higher renal cystine levels than the FVB/N strain. Moreover, C57BL/6 mice presented with pronounced histological lesions of the proximal tubules as well as a tubulopathy and progressively developed chronic renal failure. In contrast, renal dysfunction was not observed in the FVB/N strain. Conclusions. Thus, the C57BL/6 strain represents the first Ctns -/- mouse model to show clear renal defects. In addition to highlighting the influence of genetic background on phenotype, the C57BL/6 Ctns -/- mice represent a useful model for further understanding cystinosin function in the kidney and, specifically, in the proximal tubules. © 2009 The Author.
Robert L.,French Institute of Health and Medical Research |
Robert L.,Universites Montpellier i et Ii |
Senechal A.,French Institute of Health and Medical Research |
Senechal A.,Universites Montpellier i et Ii |
And 9 more authors.
Ophthalmic Research | Year: 2011
Choroideremia is an X-linked, progressive photoreceptor degeneration disorder due to mutations in CHM. In addition to an atrophy of the outer retina, affected individuals present with a characteristic atrophy of the choroid. To search for a canine model, we screened the CHM gene of 37 dogs (22 breeds) with various forms of retinal dystrophies. We found 21 variations in 13 breeds (17 detected in only one breed and 4 shared by two or more) with 43% segregating in the same pedigree, a Great Dane female and a female offspring. Of particular interest were an exonic missense variation and a 3-bp intronic deletion near a splice acceptor site. However, although not detected in unrelated healthy Great Danes, these variants were nonpathogenic since they did not segregate with the disease phenotype in the pedigree. These results suggest that a CHM dog model may not be viable, as is the case for mouse and zebrafish. Copyright © 2010 S. Karger AG.
Sayan A.E.,University of Leicester |
Sayan A.E.,University of Southampton |
Stanford R.,University of Leicester |
Vickery R.,University of Leicester |
And 12 more authors.
Oncogene | Year: 2012
Fos-related antigen 1 (Fra-1) is a Fos family member overexpressed in several types of human cancers. Here, we report that Fra-1 is highly expressed in the muscle-invasive form of the carcinoma of the bladder (80%) and to a lesser extent in superficial bladder cancer (42%). We demonstrate that in this type of cancer Fra-1 is regulated via a C-terminal instability signal and C-terminal phosphorylation. We show that manipulation of Fra-1 expression levels in bladder cancer cell lines affects cell morphology, motility and proliferation. The gene coding for AXL tyrosine kinase is directly upregulated by Fra-1 in bladder cancer and in other cell lines. Importantly, our data demonstrate that AXL mediates the effect of Fra-1 on tumour cell motility but not on cell proliferation. We suggest that AXL may represent an attractive therapeutic target in cancers expressing high Fra-1 levels. © 2012 Macmillan Publishers Limited All rights reserved.
Cattoni D.I.,Universites Montpellier i et Ii |
Le Gall A.,Universites Montpellier i et Ii |
Nollmann M.,Universites Montpellier i et Ii
Current Biology | Year: 2014
Two new studies reveal the main actors involved in the resolution and segregation of newly replicated origins in bacteria. These results have important implications for our understanding of the mechanisms involved in precisely coordinating chromosome organization, segregation and replication. © 2014 Elsevier Ltd.