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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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Ankyrin-B but not -G is expressed in the lens. (a) Immunoblot of brain and lens lysates using antibodies against ankyrin-B or -G. The molecular weight markers are indicated on the left. (b) Longitudinal noncentral section of 9-mo-old mouse lens stained with antibodies against ankyrin-B. (c) Same as b, but anterior region showing expression of ankyrin-B in the epithelium but not the capsule. (d) P12 longitudinal lens section showing that the lens fiber membranes neighboring the capsule do not express ankyrin-B. The capsule position is indicated.
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fig5: Ankyrin-B but not -G is expressed in the lens. (a) Immunoblot of brain and lens lysates using antibodies against ankyrin-B or -G. The molecular weight markers are indicated on the left. (b) Longitudinal noncentral section of 9-mo-old mouse lens stained with antibodies against ankyrin-B. (c) Same as b, but anterior region showing expression of ankyrin-B in the epithelium but not the capsule. (d) P12 longitudinal lens section showing that the lens fiber membranes neighboring the capsule do not express ankyrin-B. The capsule position is indicated.

Mentions: NrCAM, as well as other L1 subfamily members, have been shown to interact with the cytoskeletal linker proteins of the ankyrin family that associate via spectrin with F-actin (Davis and Bennett, 1994; Tuvia et al., 1997; Jefford and Dubreuil, 2000). To study whether the interaction between NrCAM and ankyrin is important for the development of lens structure, we first analyzed the expression of ankyrins in lens. To date, there are three different ankyrin genes known. Western blot analysis using a polyclonal antibody against ankyrins previously revealed that lens ankyrin did not comigrate with erythrocyte ankyrin, but instead had the molecular weight as would be expected of ankyrin-B (Dola et al., 1990). Consistently, specific monoclonal antibodies confirm the presence of ankyrin-B, but not ankyrin-G, in the lens (Fig. 5 a). Examination of the staining pattern of ankyrin-B in the secondary lens fibers by immunohistological methods (Fig. 5 b) shows that the pattern of localization matches that of NrCAM (Fig. 3 c). Like NrCAM, ankyrin-B is also not expressed at the cell membranes of fiber cells contacting the capsule, nor in the capsule itself (Fig. 5 d); however, ankyrin-B is expressed in the epithelial cells (Fig. 5 c). This localization of ankyrin-B makes an interaction between these two proteins in lens fiber cells likely.


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)

Ankyrin-B but not -G is expressed in the lens. (a) Immunoblot of brain and lens lysates using antibodies against ankyrin-B or -G. The molecular weight markers are indicated on the left. (b) Longitudinal noncentral section of 9-mo-old mouse lens stained with antibodies against ankyrin-B. (c) Same as b, but anterior region showing expression of ankyrin-B in the epithelium but not the capsule. (d) P12 longitudinal lens section showing that the lens fiber membranes neighboring the capsule do not express ankyrin-B. The capsule position is indicated.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196853&req=5

fig5: Ankyrin-B but not -G is expressed in the lens. (a) Immunoblot of brain and lens lysates using antibodies against ankyrin-B or -G. The molecular weight markers are indicated on the left. (b) Longitudinal noncentral section of 9-mo-old mouse lens stained with antibodies against ankyrin-B. (c) Same as b, but anterior region showing expression of ankyrin-B in the epithelium but not the capsule. (d) P12 longitudinal lens section showing that the lens fiber membranes neighboring the capsule do not express ankyrin-B. The capsule position is indicated.
Mentions: NrCAM, as well as other L1 subfamily members, have been shown to interact with the cytoskeletal linker proteins of the ankyrin family that associate via spectrin with F-actin (Davis and Bennett, 1994; Tuvia et al., 1997; Jefford and Dubreuil, 2000). To study whether the interaction between NrCAM and ankyrin is important for the development of lens structure, we first analyzed the expression of ankyrins in lens. To date, there are three different ankyrin genes known. Western blot analysis using a polyclonal antibody against ankyrins previously revealed that lens ankyrin did not comigrate with erythrocyte ankyrin, but instead had the molecular weight as would be expected of ankyrin-B (Dola et al., 1990). Consistently, specific monoclonal antibodies confirm the presence of ankyrin-B, but not ankyrin-G, in the lens (Fig. 5 a). Examination of the staining pattern of ankyrin-B in the secondary lens fibers by immunohistological methods (Fig. 5 b) shows that the pattern of localization matches that of NrCAM (Fig. 3 c). Like NrCAM, ankyrin-B is also not expressed at the cell membranes of fiber cells contacting the capsule, nor in the capsule itself (Fig. 5 d); however, ankyrin-B is expressed in the epithelial cells (Fig. 5 c). This localization of ankyrin-B makes an interaction between these two proteins in lens fiber cells likely.

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