Targeted ablation of NrCAM or ankyrin-B results in disorganized lens fibers leading to cataract formation

The NgCAM-related cell adhesion molecule (NrCAM) is an immunoglobulin super family member of the L1 subgroup that interacts intracellularly with ankyri ns. We reveal that the absence of NrCAM causes the formation of mature cata racts in the mouse, whereas significant pathfinding errors of commissural a xons at the midline of the spinal cord or of proprioceptive axon collateral s are not detected. Cataracts, the most common cause of visual impairment, are generated in NrCAM-deficient mice by a disorganization of lens fibers, followed by cellular disintegration and accumulation of cellular debris. Th e disorganization of fiber cells becomes histologically distinct during lat e embryonic development and includes abnormalities of the cytoskeleton and of connexin50-containing gap junctions. Furthermore, analysis of lenses of ankyrin-B mutant mice also reveals a disorganization of lens fibers at post natal day 1, indistinguishable from that generated by the absence of NrCAM, indicating that NrCAM and ankyrin-B are required to maintain contact betwe en lens fiber cells. Also, these studies provide genetic evidence of an int eraction between NrCAM and ankyrin-B.