Recombinant Mouse Notch-3 Fc Chimera Protein, CF

Mouse Notch-3 is part of the Notch family of type I transmembrane glycoproteins involved in a number of early-event developmental processes (1). The extracellular domain of Notch receptors interact with the extracellular domain of transmembrane ligands Jagged, Delta, and Serrate expressed on the surface of a neighboring cell. In both vertebrates and invertebrates, Notch signaling is important for specifying cell fates and for defining boundaries between different cell types. The Notch molecule is synthesized as a 2318 amino acid (aa) precursor that contains an 39 aa signal sequence, a 1603 aa extracellular region, a 20 aa transmembrane (TM) segment and a 655 aa cytoplasmic domain. The large Notch extracellular domain has 34 EGF-like repeats followed by three notch/Lin-12 repeats (LNR) (2). The 11^th and 12^th EGF-like repeats of Notch have been shown to be both necessary and sufficient for binding the ligands Serrate and Delta, in Drosophila (3). Notch-3 has the same biochemical mechanism of signal tranduction as Notch-1, where a series of cleavage events result in the release of the Notch intracellular domain (NICD). NICD translocates into the nucleus and initiates transcription of Notch-responsive genes (4). Thus Notch acts as both a ligand-binding receptor and a nuclear factor that regulates transcription.

Notch-3 is predominantly expressed in the developing central nervous system of mice (2). Mutations in Notch-3 in humans cause an autosomal dominant condition called CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). This disorder is characterized by recurrent ischemic strokes at an early age without any underlying vascular risk and progressive dementia. Nearly all mutations leading to this disorder are clustered in the first 5 EGF repeats of the Notch-3 gene (5). Mouse Notch-3 shows 90% aa identity to human Notch-3 and 96% to rat Notch-3 over the entire protein.