Functional conservation of Notch1 and Notch2 intracellular domains Matthew Kraman and Brent McCright Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration Bethesda, Maryland, USA 1 Correspondence: E-mail: mccright@cber.fda.gov <h3>SPECIFIC AIMS</h3> Notch1 and Notch2 are structurally conserved essential genes that are critical for the development of multiple organ systems in mammals. We hypothesized that amino acid differences in their intracellular domains (ICDs) could be responsible for exerting the functional differences that have been observed between the Notch1 and Notch2 receptors in vitro. To analyze the function of the Notch ICD in vivo, we created mice that contained a targeted mutation that replaces the nonconserved region of the Notch2 ICD with the homologous region of Notch1. <h3>PRINCIPAL FINDINGS</h3> <h3>1. Creation of mice expressing a Notch2-Notch1 fusion protein</h3> A targeting construct was made to replace the C-terminal 426 amino acids of the Notch2 ICD with the homologous region of Notch 1 (<h3>Fig. 1</h3> ). The genomic structure of both genes is highly conserved in the C-terminus of the ICD region even though the peptide sequence is not (37% identical; 137/426). In both genes, genomic DNA encoding the region from the sixth ankyrin repeat
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Functional conservation of Notch1 and Notch2 intracellular domains
Kraman, Matthew; McCright, Brent
Follow The FASEB Journal
, Volume 19 (10): 1311
Fed of American Socs for Experimental Biology – Aug 1, 2005
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