|Institutional Source||Beutler Lab|
|Gene Name||SPARC-like 1|
|Synonyms||Ecm2, mast9, Sc1, hevin|
|Is this an essential gene?||Non essential (E-score: 0.000)|
|Stock #||R0007 (G1)|
|Chromosomal Location||104079111-104113733 bp(-) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||T to A at 104087080 bp|
|Amino Acid Change||Glutamine to Leucine at position 523 (Q523L)|
|Ref Sequence||ENSEMBL: ENSMUSP00000031249 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000031249]|
|Predicted Effect||probably damaging
AA Change: Q523L
PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
AA Change: Q523L
|Meta Mutation Damage Score||0.6706|
|Coding Region Coverage||
|Validation Efficiency||95% (54/57)|
|MGI Phenotype||Strain: 2153047
PHENOTYPE: Mice homozygous for a targeted null mutation exhibit no discernable phenotype; mice are viable and fertile with normal histology and survival. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Sparcl1||
|Protein Function and Prediction|
Sparcl1 encodes Hevin/Sc1, an matricellular secreted glycoprotein in the SPARC family (1). Hevin has three major domains: an N-terminal acidic domain, a follistatin-like domain, and the extracellular calcium-binding domain (1). The follistain-like domain is homologous to a domain in follistatin, a protein that inhibits members of the TGF-β superfamily (1). Hevin has been shown to inhibit the attachment and spreading of endothelial cells and to reduce focal adhesion formation by endothelial cells (2). Therefore, the proposed function of hevin is to modulate cell migration. Girard and Springer propose that hevin participates in lymphocyte transendothelial migration and might alter vascular permeability (2). The related protein, SPARC, functions as a cell cycle inhibitor, de-adhesive protein, a regulator of growth factor activity, and modulatory cell-matrix interactions (3).
Northern blot analysis detected expression of Sparcl1 in lymph node, brain, heart, lung, skeletal muscle, ovary, small intestine, and colon, with lower levels in placenta, pancreas, testis, spleen, and thymus, and no expression in kidney, liver, and peripheral blood leukocytes (4).
Homozygotes exhibit stunted and less branched processes extending from extending from Purkinje cell bodies compared to in wild-type mice and exhibit an increase in glial cells compared to in wild-type mice (5).
involves: 129S1/Sv * C57BL/6
Mice homozygous for a targeted null mutation exhibit no discernable phenotype; mice are viable and fertile with normal histology and survival (6).
1. Sullivan, M. M., and Sage, E. H. (2004) Hevin/SC1, a Matricellular Glycoprotein and Potential Tumor-Suppressor of the SPARC/BM-40/Osteonectin Family. Int J Biochem Cell Biol. 36, 991-996.
2. Girard, J. P., and Springer, T. A. (1996) Modulation of Endothelial Cell Adhesion by Hevin, an Acidic Protein Associated with High Endothelial Venules. J Biol Chem. 271, 4511-4517.
3. Brekken, R. A., Sullivan, M. M., Workman, G., Bradshaw, A. D., Carbon, J., Siadak, A., Murri, C., Framson, P. E., and Sage, E. H. (2004) Expression and Characterization of Murine Hevin (SC1), a Member of the SPARC Family of Matricellular Proteins. J Histochem Cytochem. 52, 735-748.
4. Girard, J. P., and Springer, T. A. (1995) Cloning from Purified High Endothelial Venule Cells of Hevin, a Close Relative of the Antiadhesive Extracellular Matrix Protein SPARC. Immunity. 2, 113-123.
5. Weaver, M. S., Workman, G., Cardo-Vila, M., Arap, W., Pasqualini, R., and Sage, E. H. (2010) Processing of the Matricellular Protein Hevin in Mouse Brain is Dependent on ADAMTS4. J Biol Chem. 285, 5868-5877.
|Science Writer||Anne Murray|