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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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The absence of ankyrin-B causes similar lens fiber disorganization as the absence of NrCAM. (a and b) Longitudinal section through a P0.5 ankyrin-B−/− lens, HE stained. Arrows, rounded abnormal shaped cells. (c and d) Longitudinal section through a P0.5 ankyrin-B+/+ sibling lens, HE stained. (e) Longitudinal section through a P1 ankyrin-B−/− lens, stained with the F-actin stain FITC-phalloidin. Arrows, aggregates of F-actin.
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fig6: The absence of ankyrin-B causes similar lens fiber disorganization as the absence of NrCAM. (a and b) Longitudinal section through a P0.5 ankyrin-B−/− lens, HE stained. Arrows, rounded abnormal shaped cells. (c and d) Longitudinal section through a P0.5 ankyrin-B+/+ sibling lens, HE stained. (e) Longitudinal section through a P1 ankyrin-B−/− lens, stained with the F-actin stain FITC-phalloidin. Arrows, aggregates of F-actin.

Mentions: For this reason, we reanalyzed whether ankyrin-B−/− mice previously generated (Scotland et al., 1998) also develop a disorganized lens. Since most ankyrin-B−/− mice do not survive beyond P1, we had to analyze the lenses of ankyrin-B−/− mice at this stage. Interestingly, the organization of secondary lens fibers at the anterior pole was severely disturbed in the ankyrin-B−/− lenses (Fig. 6 , a and b), closely resembling the lenses of NrCAM−/− mice at a similar stage (Fig. 4, b and c). In contrast, the lenses of control siblings revealed an ordered arrangement of lens fibers (Fig. 6, c and d). Even though the lens epithelium strongly expresses ankyrin-B, its absence had no significant effect on the organization of epithelial cells. The observation that the absence of the cytoskeletal linker protein ankyrin-B results in a disorganization of lens fiber cells similar to that observed in the absence of NrCAM suggests that NrCAM mediated cell–cell contact between lens fibers requires a direct link to the actin cytoskeleton.


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)

The absence of ankyrin-B causes similar lens fiber disorganization as the absence of NrCAM. (a and b) Longitudinal section through a P0.5 ankyrin-B−/− lens, HE stained. Arrows, rounded abnormal shaped cells. (c and d) Longitudinal section through a P0.5 ankyrin-B+/+ sibling lens, HE stained. (e) Longitudinal section through a P1 ankyrin-B−/− lens, stained with the F-actin stain FITC-phalloidin. Arrows, aggregates of F-actin.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: The absence of ankyrin-B causes similar lens fiber disorganization as the absence of NrCAM. (a and b) Longitudinal section through a P0.5 ankyrin-B−/− lens, HE stained. Arrows, rounded abnormal shaped cells. (c and d) Longitudinal section through a P0.5 ankyrin-B+/+ sibling lens, HE stained. (e) Longitudinal section through a P1 ankyrin-B−/− lens, stained with the F-actin stain FITC-phalloidin. Arrows, aggregates of F-actin.
Mentions: For this reason, we reanalyzed whether ankyrin-B−/− mice previously generated (Scotland et al., 1998) also develop a disorganized lens. Since most ankyrin-B−/− mice do not survive beyond P1, we had to analyze the lenses of ankyrin-B−/− mice at this stage. Interestingly, the organization of secondary lens fibers at the anterior pole was severely disturbed in the ankyrin-B−/− lenses (Fig. 6 , a and b), closely resembling the lenses of NrCAM−/− mice at a similar stage (Fig. 4, b and c). In contrast, the lenses of control siblings revealed an ordered arrangement of lens fibers (Fig. 6, c and d). Even though the lens epithelium strongly expresses ankyrin-B, its absence had no significant effect on the organization of epithelial cells. The observation that the absence of the cytoskeletal linker protein ankyrin-B results in a disorganization of lens fiber cells similar to that observed in the absence of NrCAM suggests that NrCAM mediated cell–cell contact between lens fibers requires a direct link to the actin cytoskeleton.

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