Extracellular Matrix-Associated Protein Sc1 Is Not Essential for Mouse Development

Abstract

Sc1 is an extracellular matrix-associated protein whose function is unknown. During early embryonic development, Sc1 is widely expressed, and from embryonic day 12 (E12), Sc1 is expressed primarily in the developing nervous system. This switch in Sc1 expression at E12 suggests an importance for nervous-system development. To gain insight into Sc1 function, we used gene targeting to inactivate mouse Sc1. The Sc1-null mice showed no obvious deficits in any organs. These mice were born at the expected ratios, were fertile, and had no obvious histological abnormalities, and their long-term survival did not differ from littermate controls. Therefore, the function of Sc1 during development is not critical or, in its absence, is subserved by another protein.Molecules of the extracellular matrix (ECM) show definite patterns of spatial and temporal regulation and are critical for a wide range of events during development. For example, development of the nervous system requires ECM components for axonal target finding, neural crest guidance, and normal tissue morphogenesis (33,36,37). While the ECM is a critical modulator of spatial and temporal information during development, there are many matrix components whose function are unknown. One such protein is Sc1.Sc1 is abundantly expressed in the adult nervous system and heart (11,17,21). Sc1 is also found in the high endothelial venules of the immune system, where it has been suggested to function in lymphocyte extravasation (6). Sc1 is a member of a gene family that includes Sparc, testican, Qr1, agrin, and follistatin (1,8,25,35). The similarity of Sc1 to members of this family, which varies from 30 to 65% amino acid identity, is by virtue of a 230-amino-acid stretch at the carboxyl terminus of the molecule, suggesting functional conservation of this region. However, Sc1 also contains a unique amino terminus (ϳ400 amino acids), which shows no similarity to any protein sequence in the current gene databases. The region of Sc1 encoding the carboxy terminus contains a similar exon structure to that of Sparc, suggesting that these two genes evolved from a common ancestral gene and may have related functions (16).Sparc is highly expressed in bone (hence its alternative name, osteonectin), as well as a number of other tissues (12,20,23,32). Sparc has been implicated in angiogenesis (27, 30), and both Sc1 and Sparc are associated with astrocytes in the adult rodent brain (17,19). Because astrocytes are required for maintenance of the blood-brain barrier and a nutrient supply interface between capillary blood supply and neurons (34), the presence of Sc1 and Sparc in astrocytes supports a role in angiogenesis. The upregulation of Sc1 and Sparc after neural injury (4, 17) may also suggest a role in tissue remodeling or repair.Sparc is able to modulate platelet-derived growth factor binding to its receptor, and this affects cell cycle progression in certain endothelial cell lines (2, 3); the follistatin-like module present in Sparc (and Sc1) may be responsible for this cytokine reg...

Localization of the Extracellular Matrix Protein SC1 Coincides with Synaptogenesis During Rat Postnatal Development

“…SC1-null mice appear normal with no signs of neural irregularities [26]. However, further studies indicate subtle abnormalities in the inflammatory response and dermal extracellular matrix deposition [27,28].…”

Expression and Characterization of Murine Hevin (SC1), a Member of the SPARC Family of Matricellular Proteins

“…The function of hevin in the regulation of tissue growth, reaction to injury, and remodeling is not clear, especially with the claim that hevin-null mice lack a discernable phenotype and display no alterations in SPARC levels, in comparison to wild-type mice (McKinnon et al 2000). SPARC-null mice also do not show major alterations in hevin, as determined by IHC (RAB, unpublished observation).…”

SC1/Hevin

“…Furthermore, expression of SC1/hevin is associated with the migration of myotomes during somitogenesis in early mouse embryos and undergoes a rapid down-regulation just before myotome emigration from the somitic environment (9). In another line of work, SC1/hevin was shown to bind to Blymphocyte precursors (10) and to augment B cell lymphopoiesis (11,12), effects that are mediated by the N-terminal acidic domain I. Gene targeting of SC1 in mouse did not show any obvious phenotype (13), a finding that is not too surprising considering the number of members of the BM-40 family that may play a compensatory role.…”