Bascule transatlantique : perspectives 1998-1999 pour l'économie mondiale.

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Fidgetin-Like1 Is a Strong Candidate for a Dynamic Impairment of Male Meiosis Leading to Reduced Testis Weight in Mice

Chantier qualité GAInternational audienceBACKGROUND: In a previous work, using an interspecific recombinant congenic mouse model, we reported a genomic region of 23 Mb on mouse chromosome 11 implicated in testis weight decrease and moderate teratozoospermia (∼20-30%), a Quantitative Trait Locus (QTL) called Ltw1. The objective of the present study is to identify the gene underlying this phenotype. RESULTS: In the present study, we refined the QTL position to a 5 Mb fragment encompassing only 11 genes. We showed that the low testis weight phenotype was due to kinetic alterations occurring during the first wave of the spermatogenesis where we could point out to an abnormal lengthening of spermatocyte prophase. We identify Fidgetin-like 1 (Fignl1) as the gene underlying the phenotype, since if fulfilled both the physiological and molecular characteristics required. Indeed, amongst the 11 positional candidates it is the only gene that is expressed during meiosis at the spermatocyte stage, and that presents with non-synonymous coding variations differentiating the two mouse strains at the origin of the cross. CONCLUSIONS: This work prompted us to propose Fignl1 as a novel actor in mammal's male meiosis dynamics which has fundamental interest. Besides, this gene is a new potential candidate for human infertilities caused by teratozoospermia and blockades of spermatogenesis. In addition this study demonstrates that interspecific models may be useful for understanding complex quantitative traits

la tourmente financière: Perspectives 1998-1999 pour l'économie mondiale.

Cette publication n'a pas de résumé

The prion or the related Shadoo protein is required for early mouse embryogenesis

AbstractThe prion protein PrP has a key role in transmissible spongiform encephalopathies but its biological function remains largely unknown. Recently, a related protein, Shadoo, was discovered. Its biological properties and brain distribution partially overlap that of PrP. We report that the Shadoo-encoding gene knockdown in PrP-knockout mouse embryos results in a lethal phenotype, occurring between E8 and E11, not observed on the wild-type genetic background. It reveals that these two proteins play a shared, crucial role in mammalian embryogenesis, explaining the lack of severe phenotype in PrP-knockout mammals, an appreciable step towards deciphering the biological role of this protein family

Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

<p>Abstract</p> <p>Background</p> <p>The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages.</p> <p>Results</p> <p>Only subtle transcriptomic differences resulting from the <it>Prnp </it>knockout could be evidenced, beside <it>Prnp </it>itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal <it>Prnp </it>disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences.</p> <p>Conclusions</p> <p>These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.</p

Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria.

International audienceCongenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR

Contribution à l étude du rôle biologique des gènes de la famille Prion

La protéine Prion, PrP, est connue pour son implication dans les encéphalopathies spongiformes transmissibles. Cette protéine appartient à une famille de glycoprotéines membranaires qui comprend également la protéine Shadoo. Le rôle biologique de ces deux protéines reste peu connu. L objectif de cette thèse a été de d étudier le rôle de Shadoo par dérégulation de l'expression de son gène chez la souris et le poisson zèbre. Les résultats montrent que les protéines PrP et Shadoo interviendraient chez la souris dans le développement précoce de l embryon, notamment dans la mise en place du placenta. Chez le poisson zèbre, le gène Shadoo1, exprimé précocement, aurait aussi un rôle dans le développement embryonnaire. Ces données apportent un éclairage nouveau sur le rôle de Shadoo et de la PrP dans le développement embryonnaire des vertébrés.The prion protein, PrP, is known for its involvement in transmissible spongiform emcephalopathies. This protein belongs to a membrane-associated glycoprotein family that comprises also the Shadoo protein. The biological role of these two proteins remains poorly understood. The aim of this thesis was to study the function of Shadoo by deregulating its gene expression in mice and zebrafish. The results indicate that PrP and Shadoo appear to be involved in early mouse embryonic development, and more precisely in the placenta development. In zebrafish, expressed Shaddo1-encoding gene is also involved in early embryogenesis. These data highlight a new role of PrP and Shadoo in vertebrate embryonic development.VERSAILLES-BU Sciences et IUT (786462101) / SudocSudocFranceF

Topaz1 suppression disrupts the expression of testicular long non-coding RNAs during murine spermatogenesis

International audienc

Introduction d'une étiquette FLAG à la protéine TOPAZ1 par recombinaison homologue directement dans le zygote

National audienc

Liver Abscess Caused by Infection with Community-Acquired Klebsiella quasipneumoniae subsp. quasipneumoniae

We report a case of pyogenic liver abscess caused by community-acquired Klebsiella quasipneumoniae subsp. quasipneumoniae. The infecting isolate had 2 prominent features of hypervirulent K. pneumoniae strains: the capsular polysaccharide synthesis region for K1 serotype and the integrative and conjugative element ICEKp1, which encodes the virulence factors yersiniabactin, salmochelin, and RmpA