French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Lamin a truncation in hutchinson-gilford progeria

Abstract: Little is known about the pathophysiology of human senescence. Hutchinson-Gilford progeria syndrome (HGPS) is an exceedingly rare but typical progeria, clinically characterized by postnatal growth retardation, midface hypoplasia, micrognathia, premature atherosclerosis, absence of subcutaneous fat,

GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle

Abstract: For survival, embryonic motoneurons in vertebrates depend on as yet undefined neurotrophic factors present in the limb bud. Members of the neurotrophin family are currently the best candidates for such neurotrophic factors, but inactivation of their receptor genes leads to only partial loss of motoneurons, which suggests that other factors are involved. Glial cell line-derived neurotrophic factor (GDNF), originally identified as a trophic factor specific for dopaminergic neurons, was found to be 75-fold more potent than the neurotrophins in supporting the survival of purified embryonic rat motoneurons in culture. GDNF messenger RNA was found in the immediate vicinity of motoneurons during the period of cell death in development. In vivo, GDNF rescues and prevents the atrophy of facial motoneurons that have been deprived of target-derived survival factors by axotomy. GDNF may therefore be a physiological trophic factor for spinal motoneurons. Its potency and specificity in vitro and in vivo also make it a good candidate for treatment of motoneuron disease.

The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus

Abstract: RETINOIC acid is a vitamin A derivative with striking effects on development and cell differentiation1–3. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized4–8 and indirect evidence suggests that they have distinct roles9–11. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions12–13. Because the RARα gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21–qll–22) translocation specifically associated with APL15, we analysed RARα gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RARα gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RARα fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RARα and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor α in leukaemogenesis.