Inserm/Université IRNEM - IFR 94

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Réponses affichées : 7

  Normal Immune System Development in Mice Lacking the Deltex-1 RING Finger Domain
STORCK S, DELBOS F, STADLER N, THIRION-DELALANDE C, BERNEX F, VERTHUY C, FERRIER P, WEILL JC, REYNAUD CA
2005 - Mol. Cell. Biol. 25(4):1437-1445
The Notch signaling pathway controls several cell fate decisions during lymphocyte development, from T-cell lineage commitment to the peripheral differentiation of B and T lymphocytes. Deltex-1 is a RING finger ubiquitin ligase which is conserved from Drosophila to humans and has been proposed to be a regulator of Notch signaling. Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment. Deltex-1 was also found to be highly expressed in germinal-center B cells. To investigate the physiological function of Deltex-1, we generated a mouse strain lacking the Deltex-1 RING finger domain, which is essential for its ubiquitin ligase activity. Deltex-1(Delta/Delta) mice were viable and fertile. A detailed histological analysis did not reveal any defects in major organs. T- and B-cell development was normal, as were humoral responses against T-dependent and T-independent antigens. These data indicate that the Deltex-1 ubiquitin ligase activity is dispensable for mouse development and immune function. Possible compensatory mechanisms, in particular those from a fourth Deltex gene identified during the course of this study, are also discussed.
Unité(s) : U373, Animalerie IRNEM
 
  Naive T cells proliferate strongly in neonatal mice in response to self-peptide/self-MHC complexes
LE CAMPION A, BOURGEOIS C, LAMBOLEZ F, MARTIN B, LEAUMENT S, DAUTIGNY N, TANCHOT C, PENIT C, LUCAS B
2002 - Proc. Nat. Acad. Sci. USA 99(7):4538-4543
Adult naive T cells, which are at rest in normal conditions, proliferate strongly when transferred to lymphopenic hosts. In neonates, the first mature thymocytes to migrate to the periphery reach a compartment devoid of preexisting T cells. We have extensively analyzed the proliferation rate and phenotype of peripheral T cells from normal C57BL/6 and T cell antigen receptor transgenic mice as a function of age. We show that, like adult naive T cells transferred to lymphopenic mice, neonatal naive T cells proliferate strongly. By using bone-marrow transfer and thymic-graft models, we demonstrate that the proliferation of the first thymic emigrants reaching the periphery requires T cell antigen receptor-self-peptide/self-MHC interactions and is regulated by the size of the peripheral T cell pool.
Unité(s) : Animalerie IRNEM, U345
 
  Quantitative and qualitative adjustment of thymic T cell production by clonal expansion of premigrant thymocytes
LE CAMPION A, LUCAS B, DAUTIGNY N, LEAUMENT S, VASSEUR F, PENIT C
2002 - J. Immunol. 168(4):1664-1671
In normal mice, single-positive thymocytes proliferate before being exported into the peripheral T cell pool. We measured the in vivo proliferation rates of mature thymocytes in several TCR transgenic mice. Different monoclonal TCR transgenic single-positive thymocytes proliferated at different rates in a given MHC context. Conversely, mature thymocytes expressing a given TCR, generated in mice of different MHC haplotypes, also showed different rates of proliferation. In p59(fyn)-deficient mice, the proliferation rate of mature thymocytes was diminished. Thus, premigrant thymocyte expansion is TCR mediated and depends on TCR affinity for self peptide/MHC ligands. In addition, we show that mature thymocyte expansion is clonotypic, increases the daily thymic T cell output, and modifies the TCR repertoire of newly produced T cells.
Unité(s) : Animalerie IRNEM, U345
 
  Conversion of naive T cells to a memory-like phenotype in lymphopenic hosts is not related to a homeostatic mechanism that fills the peripheral naive T cell pool
TANCHOT C, LE CAMPION A, MARTIN B, LEAUMENT S, DAUTIGNY N, LUCAS B
2002 - J. Immunol. 168(10):5042-5046
To examine directly whether a limited number of naive T cells transferred to lymphopenic hosts can truly fill the peripheral naive T cell pool, we compared the expansion and phenotype of naive T cells transferred to three different hosts, namely recombination-activating gene-deficient mice, CD3epsilon-deficient mice, and irradiated normal mice. In all three recipients, the absolute number of recovered cells was much smaller than in normal mice. In addition, transferred naive T cells acquired a memory-like phenotype that remained stable with time. Finally, injected cells were rapidly replaced by host thymic migrants in irradiated normal mice. Only continuous output of naive T cells by the thymus can generate a full compartment of truly naive T cells. Thus, conversion of naive T cells to a memory-like phenotype in lymphopenic hosts is not related to a homeostatic mechanism that fills the peripheral naive T cell pool.
Unité(s) : Animalerie IRNEM, U345
 
  Naive cd4(+) lymphocytes convert to anergic or memory-like cells in t cell-deprived recipients
TANCHOT C, LE CAMPION A, LEAUMENT S, DAUTIGNY N, LUCAS B
2001 - Eur. J. Immunol. 31(8):2256-2265
Recent demonstrations that naive T cells proliferate after transfer to lymphopenic hosts have led to the theory that active homeostatic mechanisms fill the peripheral pool of naive T cells. To extend these data, we injected naive CD4(+) T cells from AND TCR transgenic mice (H-2(b/b) or H-2(k/k)) into CD3 epsilon-deficient mice, and studied the absolute number, phenotype and functional capacities of the transferred lymphocytes, from the first days to a few months after transfer. Proliferation of naive CD4(+) T cells did not fill the peripheral naive T cell pool. Injected naive T cells acquired a memory-like phenotype that was stable with time, despite the absence of foreign antigenic stimulation. Their functional capacities were modified, enhanced or abolished depending on the MHC haplotype. Thus, "homeostatic" proliferation of naive CD4(+) T cells in T cell-deprived recipients does not regenerate the naive CD4(+) T cell pool.
Unité(s) : U345, Animalerie IRNEM
 
  Prolactin receptor knockout model: Study of maternal behavior
ALLAMANDO A, LUCAS BK, EVRA C, BINART N, KELLY PA
1999 - Sci. Techn. Anim. Lab. 24(3):191-197
We have studied pup-directed maternal behavior in mice carrying a germ line null mutation of the prolactin receptor gene. Heterozygous nulliparous and primiparous females and homozygous nulliparous females exhibit a profound deficit in maternal care when challenged with foster pups. Morris maze studies revealed normal configural learning in heterozygous and homozygous animals. Olfactory function was tested in an aversive conditioning paradigm, confirming that heterozygous and homozygous prolactin receptor mutant mice are not anosmic. This studies clearly establish the prolactin receptor as a regulator of maternal behavior. [References: 24]
Unité(s) : U344, Animalerie IRNEM
 
  From the molecular biology of prolactin and its receptor to the lessons learned from knockout mice models
GOFFIN V, BINART N, CLEMENT-LACROIX P, BOUCHARD B, BOLE-FEYSOT C, EDERY M, LUCAS BK, TOURAINE P, PEZET A, MAASKANT R, PICHARD C, HELLOCO C, BARAN N, FAVRE H, BERNICHTEIN S, ALLAMANDO A, ORMANDY C, KELLY PA
1999 - Genet. Anal.- Biomol. Eng. 15(3-5):189-201
Prolactin (PRL), a polypeptide hormone secreted mainly by the pituitary and, to a lesser extent, by peripheral tissues, affects more physiological processes than all other pituitary hormones combined since it is involved in > 300 separate functions in vertebrates. Its main actions are related to lactation and reproduction. The initial step of PRL action is the binding to a specific membrane receptor, the PRLR, which belongs to the class 1 cytokine receptor superfamily. PRL-binding sites have been identified in a number of tissues and cell types in adult animals. Signal transduction by this receptor is mediated, at least in part, by two families of signaling molecules: Janus tyrosine kinases and signal transducers and activators of transcription (STATs). Disruption of the PRLR gene has provided a new mouse model with which to identify actions directly associated with PRL or any other PRLR ligands, such as placental lactogens. To date, several different phenotypes have been analyzed and are briefly described in this review. Coupled with the SAGE technique, this PRLR knockout model is being used to qualitatively and quantitatively evaluate the expression pattern of hepatic genes in two physiological situations: transcriptomes corresponding to livers from both wild type and PRLR KO mice are being compared, and following statistical analyses, candidate genes presenting a differential profile will be further characterized. Such a new approach will undoubtedly open future avenues of research for PRL targets. To date, no pathology linked to any mutation in the genes encoding PRL or its receptor have been identified. The development of genetic models provides new opportunities to understand how PRL can participate to the development of pathologies throughout life, as for example the initiation and progression of breast cancer. [References: 98]
Unité(s) : U344, Animalerie IRNEM
 
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