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 superfamily member of the L1 subgroup that interacts intracellularly with ankyrins. We reveal that the absence of NrCAM causes the formation of mature cataracts in the mouse, whereas significant pathfinding errors of commissural axons at the midline of the spinal cord or of proprioceptive axon collaterals 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. The disorganization of fiber cells becomes histologically distinct during late 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 postnatal day 1, indistinguishable from that generated by the absence of NrCAM, indicating that NrCAM and ankyrin-B are required to maintain contact between lens fiber cells. Also, these studies provide genetic evidence of an interaction between NrCAM and ankyrin-B.
Moré
M I
MI
Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany.
Kirsch
F P
FP
Rathjen
F G
FG
D000199:Actins / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000502:physiology*; D001369:Axons / Q000378:metabolism; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology*; D017630:Connexins; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D017629:Gap Junctions; D018390:Gene Targeting; D005838:Genotype; D006720:Homozygote; D015151:Immunoblotting; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution; D000099264:Connexin 50
D000199:Actins; D017487:Ankyrins; D015815:Cell Adhesion Molecules; D017630:Connexins; D005136:Eye Proteins; D000099264:Connexin 50; C498995:Ank2 protein, mouse; C432674:Ank2 protein, rat; C491151:Nrcam protein, mouse