Neurocan is a significant component of the extracellular matrix, and its levels are modulated by a variety of factors, but mice in which the NCAN gene has been knocked out show no easily observable defects in brain development or behavior. However, a genome-wide association study published in 2011 identified Neurocan as a susceptibility factor for bipolar disorder. A more comprehensive study published in 2012 confirmed that association. The 2012 study examined correlations between NCAN alleles and various symptoms of bipolar disorder, and also examined the behavior of NCAN knockout mice. In the human subjects, it was found that NCAN genotype was strongly associated with manic symptoms but not with depressive symptoms. In the mice, the absence of functional Neurocan resulted in a variety of manic-like behaviors, which could be normalized by administering lithium.
Milev P, Maurel P, Häring M, et al. (1996). "TAG-1/axonin-1 is a high-affinity ligand of neurocan, phosphacan/protein-tyrosine phosphatase-zeta/beta, and N-CAM.". J. Biol. Chem.271 (26): 15716–23. doi:10.1074/jbc.271.26.15716. PMID8663515.
Retzler C, Göhring W, Rauch U (1996). "Analysis of neurocan structures interacting with the neural cell adhesion molecule N-CAM.". J. Biol. Chem.271 (44): 27304–10. doi:10.1074/jbc.271.44.27304. PMID8910306.
Rauch U, Clement A, Retzler C, et al. (1997). "Mapping of a defined neurocan binding site to distinct domains of tenascin-C.". J. Biol. Chem.272 (43): 26905–12. doi:10.1074/jbc.272.43.26905. PMID9341124.
Milev P, Chiba A, Häring M, et al. (1998). "High affinity binding and overlapping localization of neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta with tenascin-R, amphoterin, and the heparin-binding growth-associated molecule.". J. Biol. Chem.273 (12): 6998–7005. doi:10.1074/jbc.273.12.6998. PMID9507007.
Oleszewski M, Gutwein P, von der Lieth W, et al. (2000). "Characterization of the L1-neurocan-binding site. Implications for L1-L1 homophilic binding.". J. Biol. Chem.275 (44): 34478–85. doi:10.1074/jbc.M004147200. PMID10934197.
Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.". Nat. Biotechnol.22 (6): 707–16. doi:10.1038/nbt971. PMID15146197.