Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Université Louis Pasteur

Other

E. R. Squibb Sons, Inc.

Bristol-myers Squibb Compnay

Philippe Kastner

Pierre H Chambon

Manuel Mark

Marianne Lemeur

Andree Dierich

Philippe Gorry

Thomas Lufkin

David Lohnes

Cathy Mendelsohn

Mark Leid

The present invention is based in part on the novel observation that two different types of nuclear receptors, retinoic acid receptors (RAR) and thyroid receptors (TR) dimerize with a RX receptor (RXR) to form a heterodimer which is capable of binding to retinoic acid response elements (RARE) or thyroid receptor response elements (TRE) at physiological conditions. In addition, the present invention discloses that RXR homodimers are capable of binding to RARE's. Based on this observation, the present invention provides novel dimeric proteins, methods of identifying agents capable of binding the dimers of the present invention, methods of identifying DNA sequences capable of being bound by the dimers and methods to identify RA metabolic enzymes and proteins which are required for the activation function of nuclear receptors.

Heterodimeric nuclear receptors proteins, genes encoding same, and usage thereof

The present invention provides mice which are deficient in the normal expression of one or more members of the RAR or RXR class of receptors, to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous or homozygous for such deficiency. The present invention further provides the use of any of the above mice and cell lines in situations where the absence of at least one RAR or RXR receptors, or the normal expression thereof, is desirable.

Genetically engineered mice containing alterations in the genes encoding retinoic acid receptor proteins

The present invention is directed to mice which are genetically altered to be deficient in the normal expression of RXR.gamma., to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous or homozygous for such deficiency. The invention further provides mice and cell lines which, in addition to being deficient in RXR.gamma., are genetically altered to be deficient in the expression of RXR.alpha. and/or RXR.beta.. The present invention further provides the use of any of the above mice and cell lines in situations where the absence of RXR.gamma., or the normal expression thereof, is desirable.

Genetically engineered mice containing alterations in the gene encoding

Genetically engineered mice and cell lines containing alterations in the

Genetically engineered mice containing alterations in the genes encoding

Growing community of inventors

Strasbourg, France

Philippe Kastner