ABSTRACT
Mice carrying a homozygous germ-line mutation in the nm23-M1 gene that eliminates its protein expression and drives expression of beta-galactosidase by nm23-M1 promoter have been generated. nm23-M1 gene inactivation is not teratogenic and the pups can grow to adult age without apparent health problems. However, they undergo a growth retardation and knocked out females cannot feed their pups. Both effects are background dependent. Beta-galactosidase mapping of nm23-M1 promoter activation during embryogenesis shows that the nm23-M1 gene is principally expressed in epithelial layer of tissues which require inductive epithelial-mesenchymal interactions for their formation. In conclusion, invalidated mice could be interesting models to analyze the role of nm23-M1 on signal transduction pathway regulation, or cancer induction and proliferation.
Subject(s)
Breast/metabolism , Fetal Growth Retardation/genetics , Gene Expression Regulation, Developmental/genetics , Gene Expression Regulation, Enzymologic/genetics , Models, Animal , Nucleoside-Diphosphate Kinase , Proteins/genetics , Proteins/metabolism , Animals , Animals, Newborn , Cloning, Molecular , Female , Fetal Growth Retardation/metabolism , Mice , Mice, Knockout/embryology , Mice, Knockout/growth & development , Mice, Knockout/metabolism , NM23 Nucleoside Diphosphate Kinases , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Signal Transduction/genetics , Structure-Activity RelationshipABSTRACT
The nm23 gene family is thought to be involved in physiopathological processes such as growth, differentiation and cancer promotion, progression or metastasis. We report here the mouse nm23-M3 and nm23-M4 complementary DNA sequences and the genomic cloning, characterization and tissue expression pattern of the nm23-M2, nm23-M3 and nm23-M4 genes, in comparison with their human and rat orthologs and with the human nm23-H1 and mouse nm23-M1 genes. The organization and structure of the members of this gene family are remarkably similar in human and rodents. Accordingly, the striking similarities between the human and mouse nm23 genes enable the use of mouse transgenic and knock-out models for studying the role of nucleoside diphosphate kinase isoforms in human physiopathology.
