A5082721029- Sperm and Testicular Function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Reproductive Biology and Fertility
- Trypanosoma species research and implications
- Renal and related cancers
- Virus-based gene therapy research
- Genetic Syndromes and Imprinting
- Cystic Fibrosis Research Advances
- Genetic and Kidney Cyst Diseases
- Animal Genetics and Reproduction
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Herpesvirus Infections and Treatments
- Sexual Differentiation and Disorders
- Ubiquitin and proteasome pathways
- Cell death mechanisms and regulation
- Ion Transport and Channel Regulation
- Prenatal Screening and Diagnostics
- Metabolism, Diabetes, and Cancer
- Neonatal Respiratory Health Research
- Protein Kinase Regulation and GTPase Signaling
- Monoclonal and Polyclonal Antibodies Research
Université Paris Cité
2009-2023
Centre National de la Recherche Scientifique
2009-2023
Institut Cochin
2009-2023
Inserm
2009-2023
Délégation Paris 5
2000-2019
Sorbonne Paris Cité
2011-2019
Centre de Gestion Scientifique
2016-2019
Pitié-Salpêtrière Hospital
1996
Sorbonne Université
1996
Maternité Port Royal
1995
Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report with primary infertility due to multiple morphological abnormalities sperm flagella severe disorganization axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-exome sequencing was performed on 78 patients allowing identification 22 bi-allelic mutations in DNAH1 (n = 6), CFAP43 10), and CFAP44 6). CRISPR/Cas9 created homozygous CFAP43/44 male...
Motile cilia and sperm flagella share an extremely conserved microtubule-based cytoskeleton, called the axoneme, which sustains beating motility of both organelles. Ultra-structural and/or functional defects this axoneme are well-known to cause primary ciliary dyskinesia (PCD), a disorder characterized by recurrent respiratory tract infections, chronic otitis media, situs inversus, male infertility in most severe cases, hydrocephalus. Only recently, mutations genes encoding axonemal proteins...
The Slc26 gene family encodes several conserved anion transporters implicated in human genetic disorders, including Pendred syndrome, diastrophic dysplasia and congenital chloride diarrhea. We previously characterized the TAT1 (testis transporter 1; SLC26A8) protein specifically expressed male germ cells mature sperm showed that mouse, deletion of Tat1 caused sterility due to a lack motility, impaired capacitation structural defects flagella. Ca2+, Cl− HCO3− influxes trigger events required...
We have investigated the possibility of obtaining integration and expression a native human gene in transgenic mice. An 11-kilobase (kb) chromosomal DNA fragment including insulin (1430 base pairs) was microinjected into fertilized mouse eggs. This present genomic several developing animals. One its progeny were analyzed for foreign gene. Synthesis release revealed by detection C-peptide plasma urine. Human mRNA found pancreas but not other tissues. These findings indicate that 11-kb carries...
The annulus is a septin-based ring structure located at the junction of midpiece (MP) and principal piece (PP) spermatozoa flagellum. In mouse, deletion Septin 4, structural component sperm annulus, prevents formation leads to MP–PP disjunction, flagellar bending, asthenozoospermia male sterility. Testis anion transporter 1 (Tat1) germ cell-specific member SLC26 family co-expressed with 4 annulus. Interestingly, Tat1 null bear an atrophic causing phenotype similar that Sept4 sperm. We...
Abstract Asthenozoospermia, defined by the absence or reduction of sperm motility, constitutes most frequent cause human male infertility. This pathological condition is caused morphological and/or functional defects flagellum, which preclude proper progression. While in last decade many causal genes were identified for asthenozoospermia associated with severe flagellar defects, causes purely are still poorly defined. We describe here case an infertile man, displaying without major anomalies...
Rho GTPases, which are master regulators of both the actin cytoskeleton and membrane trafficking, often hijacked by pathogens to enable their invasion host cells. Here we report that cytotoxic necrotizing factor-1 (CNF1) toxin uropathogenic Escherichia coli (UPEC) promotes Rac1-dependent entry bacteria into Our screen for proteins involved in UPEC identifies Toll-interacting protein (Tollip) as a new interacting Rac1 its ubiquitinated forms. We show knockdown Tollip reduces CNF1-induced...
Are ICSI outcomes impaired in cases of severe asthenozoospermia with multiple morphological abnormalities the flagellum (MMAF phenotype)?Despite occasional technical difficulties, for couples MMAF do not differ from those other requiring ICSI, irrespective genetic defect.Severe asthenozoospermia, especially when associated phenotype, results male infertility. Recent findings have confirmed that a aetiology is frequently responsible this phenotype. In such situations, pregnancies can be...
Ubiquitination and proteasomal degradation have recently emerged as an additional level of regulation activated forms Rho GTPases. To characterize this novel regulatory pathway to gain insight into its biological significance, we studied the ubiquitination two constitutively Rac1, i.e. mutationally Rac1L61, tumorigenic splice variant Rac1b, which is defective for several downstream signaling pathways, including JNK activation. Whereas Rac1L61 undergoes polyubiquitination subsequent in HEK293...
Male infertility is common and complex, presenting a wide range of heterogeneous phenotypes. Although about 50% cases are estimated to have genetic component, the underlying cause often remains undetermined. Here, from whole-exome sequencing on samples 168 infertile men with asthenoteratozoospermia due severe sperm flagellum, we identified homozygous ZMYND12 variants in four unrelated patients. In cells these individuals, immunofluorescence revealed altered localization DNAH1, DNALI1, WDR66,...
Abstract Dendritic cells (DC) are professional Ag-presenting that play a major role in T cell-mediated immune responses and thymocyte differentiation. To better analyze their physiological importance, we sought to generate transgenic mice presenting conditional DC deficiency. We used strategy based on the cell-specific expression of suicide gene. The DC-targeted is obtained using HIV regulatory sequences; indirect evidence has suggested these sequences control preferential DC. gene herpes...
Transfection of the human CD4 molecule into mouse cells does not confer susceptibility to immunodeficiency virus type 1 (HIV-1) infection. Expression in transgenic mice was seen offer some new possibilities. However, T expressing either receptor, or a hybrid human/mouse receptor alone conjunction with major histocompatibility complex class I molecules, were refractory vitro HIV-1 In addition, no infection observed after vivo HIV inoculation these various lines. Injection recombinant gp160...
Members of the solute carrier 26 (SLC26) family have emerged as important players in mediating anions fluxes across plasma membrane epithelial cells, cooperation with cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Among them, SLC26A3 acts a chloride/bicarbonate exchanger, highly expressed gastrointestinal, pancreatic and renal tissues. In humans, mutations gene were shown to induce congenital chloride‐losing diarrhea (CLD), rare autosomal recessive disorder...
Abstract “Immune privilege” is defined as tissue resistance to aggression by specifically activated lymphocytes, and involves the interaction between Fas expressed on infiltrating cells ligand (FasL) constitutively target tissue. To test whether ectopic expression of FasL thyrocytes could prevent autoimmune thyroid lymphoid cells, three lines transgenic mice expressing low, intermediate, high levels functional follicular were generated. Experimental thyroiditis was induced immunization with...
The expression of the CD4 gene undergoes a complex pattern regulation during T cell development. Results obtained in transgenic mice suggest that combination proximal enhancer and silencer from is sufficient to obtain developmentally controlled along maturation. We generated expressing human cDNA under control promoter murine minimal enhancer. No other regulatory sequences, including silencer, were included. this transgene restricted mature peripheral cells, only heat-stable Ag(HSA)low/-...
The SWI/SNF chromatin remodelling complexes are important regulators of transcription; they consist large multisubunit assemblies containing either Brm or Brg1 as the catalytic ATPase subunit and a variable subset approximately 10 Brg/Brm-associated factors (BAF). Among these factors, BAF60 proteins (BAF60a, BAF60b BAF60c), which found in most complexes, thought to bridge interactions between transcription complexes. We report here on Rac-dependent process leading ubiquitination. Using...
Constitutive Fas ligand (FasL) expression by specialized cells in the body participates immune privilege status of tissues containing these cells. This property has been used to prevent rejection allogeneic grafts. Nevertheless, mechanism responsible for such protection not fully elucidated. Unfortunately, grafting FasL transgenic (TG) unsuccessful. We have generated TG mice expressing (soluble + membrane bound) on thyroid follicular (TFC), and them show that ectopic prevents allograft...