[Role of Cre-loxP-mediated conditional gene targeting in understanding the function of Notch receptors].
The Notch family of cell surface receptors and their ligands constitute an evolutionarily conserved signaling pathway that is used by invertebrates and vertebrates to regulate a broad spectrum of cell specification events through local cell interactions. After ligand binding Notch receptor undergoes proteolytic processing ultimately liberating the cytoplasmic domain of the Notch receptor which translocates to the nucleus and activates target genes. In all animal models tested, mutations in Notch genes invariably resulted in developmental abnormalities. In mammals, Notch signaling controls key stages of lymphocyte differentiation as well as activation and several abnormalities in Notch pathway have been suggested to cause human leukemias. Cre-loxP mediated conditional gene targeting significantly contributed to our current understanding of the physiological roles of different Notch family members in hematopoietic compartment. This technique helped to overcome embryonic lethality of Notch mutants providing the opportunity to inactivate specific Notch gene in adulthood.
Sitnik
Katarzyna
K
Wydział Biotechnologii, Uniwersytetu Jagiellońskiego, Kraków.
Cichy
Joanna
J
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D000013:Congenital Abnormalities / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D015321:Gene Rearrangement; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D007938:Leukemia / Q000235:genetics; D051379:Mice; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes / Q000235:genetics* / Q000502:physiology; D014714:Vertebrates / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004274:DNA, Recombinant; D029721:Drosophila Proteins; D051880:Receptors, Notch; D014157:Transcription Factors