Project Details
Projekt
Genetic analysis of nidogens during embryonic development in mice, in particular in bone development
Applicant
Dr. Bernhard Bader
Subject Area
Dermatology
Term
from 2000 to 2008
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5248618
Nidogen/entactin mediates the supramolecular organisation of basement membrane(s) (BM), a dogma in the field of BM research. Nidogen-1 and nidogen-2 represent the only known members of the nidogen gene family so far. We propose the genetic analysis of the nidogen-2 gene in mice. First, we will mutate the mouse nidogen-2 gene in ES cells by homologous recombination. This mutation will simultaneously introduce a specific deletion and insertion into the nidogen-2 gene which leads to the inactivation of nidogen-2, but will allow the analysis of the endogenous nidogen-2 promoter activity by the insertion of a lacZ reporter. Nidogen-2 mutant knockout mice will enable us to analyse the function and expression of the nidogen-2 gene during embryonic development and in adult stages. Crossing nidogen-2 mutant mice with nidogen-1 mutant mice we can generate genetically mice deficient for both nidogens. The analyses of different nidogen-deficiencies will unravel specific and redundant in vivo functions of the nidogen family which may be both BM and/or organ-specific. These studies should 1) test established models of BM formation and 2) should give new insights into the function of BM and their anchorage during embryonic development, differentiation and wound repair as well as in pathological situations (e. g. tumor growth, progression, metastasis). In the event that diseases or malformations due to nidogen-deficiencies or mutations in mice have similiarities to human diseases, these studies will help to better understand the underlying molecular mechanisms of these diseases and to establish animal models.
DFG Programme
Priority Programmes
