In the gene involves cadasil, method for diagnosing and application of international application no.

摘要

The following are claimed: (1) an isolated nucleotide sequence selected from: (a) sequences coding for human Notch3 protein and its allelic variants, (b) sequences coding for a fragment of this protein and having - 10 bases, (c) human genomic Notch3 sequences and their alleles, (d) sequences having - 90% homology with sequences (a) and (c), (e) fragments of sequences (c) or (d) having - 10 bases and (f) sequences that hybridise with a sequence of (a)-(e); (2) a nucleotide sequence selected from: (a) sequences coding for a polypeptide comprising amino acids according to a defined sequence given in the specification, (b) nucleic sequences corresponding to a defined sequence given in the specification, (c) a fragment of a sequence according to (a) or (b) comprising - 10 bases, and (d) a sequence as in (a)-(c) having = 20 point mutations; (3) a cloning or expression vector containing a nucleic acid sequence as above; (4) a cell transformed with a vector as in (3); (5) a protein or polypeptide that can be obtained by culturing a cell as in (4); (6) a therapeutic composition containing a compound with pro-Notch3 activity; (7) a therapeutic composition containing a compound with anti-Notch3 activity; (8) a method for diagnosing predisposition to neurological disorders, especially of the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) type, or diseases associated with Notch3 receptor, comprising detecting a mutation in the Notch3 gene by analysing all or part of a nucleic acid sequence corresponding to the gene; (9) a method for diagnosing predisposition to neurological disorders of the CADASIL type or diseases associated with Notch3 receptor, comprising detecting a mutated Notch3 receptor; (10) a product obtained by using cells as in (4) to screen for products that interact with wild-type or mutated Notch3 receptor as agonists or antagonists, and (11) antibodies directed against the protein of (5).