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

Moré MI, Kirsch FP, Rathjen FG - J. Cell Biol. (2001)

Bottom Line: The NgCAM-related cell adhesion molecule (NrCAM) is an immunoglobulin superfamily member of the L1 subgroup that interacts intracellularly with ankyrins.The disorganization of fiber cells becomes histologically distinct during late embryonic development and includes abnormalities of the cytoskeleton and of connexin50-containing gap junctions.Also, these studies provide genetic evidence of an interaction between NrCAM and ankyrin-B.

View Article: PubMed Central - PubMed

Affiliation: Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany.

ABSTRACT
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.

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Disorganization of F-actin and connexin50 in the absence of NrCAM. (a and b) P12 and 2.5-mo-old, respectively, lateral-anterior longitudinal section through an NrCAM−/− lens, stained with FITC-phalloidin. Filled arrowheads, examples of F-actin aggregates; open arrowheads, examples of bordering cell membranes with a still normal ordered F-actin arrangement. (c and d) 1-mo-old lenses stained with monoclonal antibodies against the gap junctional protein connexin50. (c) wild type. (d) NrCAM−/−. Arrows, con-nexin50 aggregates.
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fig7: Disorganization of F-actin and connexin50 in the absence of NrCAM. (a and b) P12 and 2.5-mo-old, respectively, lateral-anterior longitudinal section through an NrCAM−/− lens, stained with FITC-phalloidin. Filled arrowheads, examples of F-actin aggregates; open arrowheads, examples of bordering cell membranes with a still normal ordered F-actin arrangement. (c and d) 1-mo-old lenses stained with monoclonal antibodies against the gap junctional protein connexin50. (c) wild type. (d) NrCAM−/−. Arrows, con-nexin50 aggregates.

Mentions: At P12 abnormally shaped NrCAM−/− lens fibers also show irregularities in their F-actin, including some aggregates (Fig. 7 a, filled arrowheads). Other cells, mostly cells of the marginal zone that originated from dividing epithelial cells more recently, still show a normal uniform F-actin distribution below their membranes, resembling wild-type cells (Fig. 7 a, open arrowheads). By the age of 2.5 mo, the cataractous lens shows severe disorganization of the actin cytoskeleton, including F-actin aggregates below the entire membrane surface of rounded cells (Fig. 7 b, filled arrowheads). A normal F-actin arrangement only remains within cells very close to the marginal zone (Fig. 7 b, open arrowheads). The cellular debris as well as some lens fibers in the process of disintegration are devoid of F-actin (not shown). Ankyrin-B is capable of binding to spectrin, which in turn binds to actin. Consistently, the distribution of ankyrin-B in NrCAM-deficient lenses resembled that of F-actin, including aggregate formation (not shown).


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

Moré MI, Kirsch FP, Rathjen FG - J. Cell Biol. (2001)

Disorganization of F-actin and connexin50 in the absence of NrCAM. (a and b) P12 and 2.5-mo-old, respectively, lateral-anterior longitudinal section through an NrCAM−/− lens, stained with FITC-phalloidin. Filled arrowheads, examples of F-actin aggregates; open arrowheads, examples of bordering cell membranes with a still normal ordered F-actin arrangement. (c and d) 1-mo-old lenses stained with monoclonal antibodies against the gap junctional protein connexin50. (c) wild type. (d) NrCAM−/−. Arrows, con-nexin50 aggregates.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196853&req=5

fig7: Disorganization of F-actin and connexin50 in the absence of NrCAM. (a and b) P12 and 2.5-mo-old, respectively, lateral-anterior longitudinal section through an NrCAM−/− lens, stained with FITC-phalloidin. Filled arrowheads, examples of F-actin aggregates; open arrowheads, examples of bordering cell membranes with a still normal ordered F-actin arrangement. (c and d) 1-mo-old lenses stained with monoclonal antibodies against the gap junctional protein connexin50. (c) wild type. (d) NrCAM−/−. Arrows, con-nexin50 aggregates.
Mentions: At P12 abnormally shaped NrCAM−/− lens fibers also show irregularities in their F-actin, including some aggregates (Fig. 7 a, filled arrowheads). Other cells, mostly cells of the marginal zone that originated from dividing epithelial cells more recently, still show a normal uniform F-actin distribution below their membranes, resembling wild-type cells (Fig. 7 a, open arrowheads). By the age of 2.5 mo, the cataractous lens shows severe disorganization of the actin cytoskeleton, including F-actin aggregates below the entire membrane surface of rounded cells (Fig. 7 b, filled arrowheads). A normal F-actin arrangement only remains within cells very close to the marginal zone (Fig. 7 b, open arrowheads). The cellular debris as well as some lens fibers in the process of disintegration are devoid of F-actin (not shown). Ankyrin-B is capable of binding to spectrin, which in turn binds to actin. Consistently, the distribution of ankyrin-B in NrCAM-deficient lenses resembled that of F-actin, including aggregate formation (not shown).

Bottom Line: The NgCAM-related cell adhesion molecule (NrCAM) is an immunoglobulin superfamily member of the L1 subgroup that interacts intracellularly with ankyrins.The disorganization of fiber cells becomes histologically distinct during late embryonic development and includes abnormalities of the cytoskeleton and of connexin50-containing gap junctions.Also, these studies provide genetic evidence of an interaction between NrCAM and ankyrin-B.

View Article: PubMed Central - PubMed

Affiliation: Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus