Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1

Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Molecular and Cellular Neuroscience (Impact Factor: 3.84). 10/2004; 27(1):59-69. DOI: 10.1016/j.mcn.2004.06.005
Source: PubMed


The immunoglobulin superfamily adhesion molecule BEN (other names include ALCAM, SC1, DM-GRASP, neurolin, and CD166) has been implicated in the control of numerous developmental and pathological processes, including the guidance of retinal and motor axons to their targets. To test hypotheses about BEN function, we disrupted its gene via homologous recombination and analyzed the resulting mutant mice. Mice lacking BEN are viable and fertile, and display no external morphological defects. Despite grossly normal trajectories, both motor and retinal ganglion cell axons fasciculated poorly and were occasionally misdirected. In addition, BEN mutant retinae exhibited evaginated or invaginated regions with photoreceptor ectopias that resembled the "retinal folds" observed in some human retinopathies. Together, these results demonstrate that BEN promotes fasciculation of multiple axonal populations and uncover an unexpected function for BEN in retinal histogenesis.

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    • "In the retina, it was shown that several CAMs are essential for the correct extension of axons toward the exit point of the eye. Blocking the functions of L1, NrCAM or neurolin (also called BEN/DM- GRASP/ALCAM) leads to RGC axon fasciculation defects and subsequent errors in directed growth toward the optic disk (Brittis and Silver, 1995; Ott et al., 1998; Weiner et al., 2004). The next step of the RGC axons journey is the exit from the eye through the optic disk. "
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    • "For instance, Th17 cells express MCAM which binds to laminin 411 on the EC basement membrane [62], CD4+ lymphocytes express CD6 which binds to EC ALCAM [63], and ninjurin-1 on myeloid cells homotypically interacts with ninjurin-1 on inflamed ECs [64]. Mouse knockouts for Alcam[65] and Mcam (Mcamtm1Lex) have been generated, however these knockout models have not been extensively utilized to study neurological disease. "
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    • "Genetic deletion of CD166 gene was achieved by replacing its first exon with a cDNA encoding EGFP [35]. CD166 null mice are phenotypically normal and fertile [35]. We examined the prostate at 8 and 20 weeks of age and found no difference in gross anatomy and histology among WT (data not shown), CD166+/− and CD166−/− mouse prostates (Figure 5A). "
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