Mouse Chordin-like 2/CHRDL2 Antibody

Chordin-like 2 (CHL2; also known as breast tumor novel factor 1/BNF-1), is a secreted glycoprotein that has significant homology to chordin and acts as a TGF-beta superfamily antagonist (1‑3). CHL2 is a chordin family member with structural homology to CHL1 (also known as neuralin or ventroptin) (1, 2). Mouse CHL2₄₀₁ cDNA encodes a 45‑50 kDa, 426 amino acid (aa) residue precursor protein with a putative 25 aa signal peptide and a 401 aa mature segment. The mature segment contains three 63 aa cysteine-rich von Willebrand type C repeats (CRs) that are conserved among chordin family members in the spacing of 10 cysteine residues (1, 2). It also contains two potential N-linked glycosylation sites and one putative NLS that lies just proximal to the third CR repeat.

Mouse CHL2, like human CHL2, appears to undergo extensive alternate splicing. This splicing generates both secreted and intracellular forms of CHL2, and influences the type of TGF-beta superfamily member bound (1, 2). The CRs of chordin, especially CR1 and CR3, have been shown to be the functional domains for BMP binding (4). The CR1 and CR3 of CHL proteins are most similar to CR3 of chordin (1). Mature mouse and human CHL2 share 71% amino acid identity, while mouse CHL1 and -2 share 40% amino acid identity (2). Like chordin, CHL2₄₀₁ exhibits BMP inhibitory activity by directly interacting with BMP-4 and preventing binding to its receptor (1). However, another CHL2 isoform with an additional exon 9b has been shown to bind and inhibit Activin A activity as well (2). CHL2₄₀₁ is not abundantly expressed in mouse embryos, but is detected only in the chondrocytes of developing joints and in the connective tissue of reproductive organs (1). Mouse CHL2 acts to reduce the rate of matrix accumulation in mesenchymal cells, acting as a negative regulator of cartilage formation (1). In the adult mouse, CHL2 is again detected only faintly in liver, kidney, skeletal muscle and testis (1). Expression patterns in human tissue blots are distinct from those expressed in mouse (1, 2).