Centre National De La Recherche Scientifique

Other

University of Illinois

UniversitÉde Strasbourg

Gie-cerbm, Centre Europeen De Recherche En Biologie Et En Medecine (gie)

Association Pour Le Development De La Recherche En Genetique Moleculaire (aderegem)

Centre National De La Recherche Scientifique-cnrs

Association Pour La Recherche a L'igbmc (ari)

Daniel Metzger

Pierre H Chambon

John White

Huimin Zhao

John A Katzenellenbogen

Hinrich Gronemeyer

Manuel Mark

Norbert B Ghyselinck

Jean-Claude Nicolas

Jacques Bertrand Brocard

Sylvie Roux

Val&eacute;rie Dup&eacute;

Emiliana Borrelli

Pierre Chambon

Mei Li

The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor &#x3b1;, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.

Method for controlling the biological activity of a protein in a vertebrate cell

The present invention relates to a metazoan organism, with the exception of humans, and in particular a mouse, characterized in that at least one cell of this organism comprises at least one fusion protein between a recombinase Cre and a modified ligand binding domain of the nuclear estrogen receptor alpha, allowing the inactive fused recombinase to be induced by synthetic antiestrogens, but not by natural estrogens, and one or more DNA sequences of interest belonging to the genome of said organism into which one or more sites of recognition of said recombinase protein are inserted. The invention also covers the methods using said organism for the screening of medicaments, the mutagenesis and the analysis of the biological function of the DNA sequences) of interest, in particular of gene(s) of interest, such as RXR.

Transgenic mouse for targeted recombination mediated by modified Cre-ER

A DNA fragment coding for a modified nuclear glucocorticoid receptor, particularly one mutated in the region coding for the ligand binding domain, so that receptor activity is more strongly inducible by a synthetic glucocorticoid ligand than by a natural glucocorticoid ligand, is disclosed. A recombination system inducible in mammals by means of a fusion protein produced between a recombinase and the binding domain of the ligand derived from the modified glucocorticoid receptor of which the activity is more strongly inducible by synthetic glucocorticoids than by natural glucocorticoids, is also disclosed.

Modified nuclear glucocorticoid receptor, fusion protein, and DNA fragments coding for said receptor and said fusion protein

The invention relates to methods for treatment of neurological disease by administering an agent which interacts with a retinoid receptor associated with the neurological disease. The invention is also related to a method of modulating dopamine receptor synthesis by introducing an agent that interacts with a retinoid receptor associated with the dopamine receptor synthesis. The invention is further related to a transgenic animal, e.g., mouse, and mammalian cell line, which is deficient in the normal synthesis of one or more receptors of RAR&agr;, &bgr;, &ggr; and RXR, and cell line thereof.

Use of ligands for treatment of diseases responsive to retinoids

The present invention relates to a method for the preparation of a protein by yeasts. In particular, the method of the invention concerns transforming a yeast cell with a first DNA fragment encoding the protein and a second DNA fragment that encodes the receptor. The method further entails culturing the transformed yeast cell, and isolating the protein. The first DNA fragment is under control of elements providing for expression of the DNA fragment in yeast, which elements include a higher eukaryotic positive transcription control sequence consisting of a natural ligand responsive element activating sequence or a variant. The receptor is a natural nuclear receptor selected from the group consisting of receptors for steroids or for retinoids or for thyroid hormones or for vitamin D3. The receptor includes a first fragment that recognizes said ligand and a second fragment that binds to said transcriptional control sequence.

Method for the preparation of a protein by yeasts using an inducible system, vectors and correspondence transformed strains

The present invention relates to a method for the preparation of a protein by yeasts, according to which:

Method for the preparation of a protein by yeasts using an inducible

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Strasbourg, France

Daniel Metzger