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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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NrCAM-deficient mice develop cataracts and reveal reduced body weight and motor disabilities. (a) Stages of cataract development. From left to right: 1.5-mo-old NrCAM+/− lens; NrCAM−/− littermate; both lenses from 4-mo-old NrCAM−/− mouse; 9-mo-old NrCAM−/− lens; same magnification as in b. (b) Lens pairs from 11-mo-old NrCAM−/− siblings. (c) Eye of a freshly killed 4-mo-old NrCAM mouse. (d) Weights of NrCAM+/− and NrCAM−/− littermates during postnatal development. Black line and symbols, NrCAM+/− animals; light line and symbols, NrCAM−/− animals. (e) Rotarod test. The number of times the animals fell from the rod in 3 min is indicated for a nonmoving rod and the rod rotating with 6.5 rpm. Each animal was confronted without prior rod experience, first with the nonmoving rod, and after a recovery time, with the rotating rod.
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fig2: NrCAM-deficient mice develop cataracts and reveal reduced body weight and motor disabilities. (a) Stages of cataract development. From left to right: 1.5-mo-old NrCAM+/− lens; NrCAM−/− littermate; both lenses from 4-mo-old NrCAM−/− mouse; 9-mo-old NrCAM−/− lens; same magnification as in b. (b) Lens pairs from 11-mo-old NrCAM−/− siblings. (c) Eye of a freshly killed 4-mo-old NrCAM mouse. (d) Weights of NrCAM+/− and NrCAM−/− littermates during postnatal development. Black line and symbols, NrCAM+/− animals; light line and symbols, NrCAM−/− animals. (e) Rotarod test. The number of times the animals fell from the rod in 3 min is indicated for a nonmoving rod and the rod rotating with 6.5 rpm. Each animal was confronted without prior rod experience, first with the nonmoving rod, and after a recovery time, with the rotating rod.

Mentions: NrCAM-deficient mice are viable and fertile. Although the gross anatomy of the nervous system appears normal, mutant mice develop a mature cataract in their lenses that becomes visible from the outside of the eye after 4 mo of age (Fig. 2 c). This cataract development was found to be progressive: 1-mo-old mice had lenses that were slightly less translucent in the nuclear region than wild-type lenses, and 4-mo-old mice already had a white opaque lens center. 9-mo-old mice had completely opaque lenses (Fig. 2 a). However, we could observe some variance in the degree of opacity and size as demonstrated by the comparison of lenses of several 11-mo-old NrCAM−/− siblings (Fig. 2 b; compare also 4-mo-old lenses in Fig 2 a). Upon piercing mutant cataract lenses with forceps, material was extruded, indicating liquefication of secondary lens fibers. After removal of the lens capsule and its adhering tissue, only the hardened interior of primary lens fibers remained, looking not transparent like in wild-type but whitish, with an irregular surface. All adult NrCAM-deficient mice examined to date had a cataract indicating a penetrance of 100%.


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)

NrCAM-deficient mice develop cataracts and reveal reduced body weight and motor disabilities. (a) Stages of cataract development. From left to right: 1.5-mo-old NrCAM+/− lens; NrCAM−/− littermate; both lenses from 4-mo-old NrCAM−/− mouse; 9-mo-old NrCAM−/− lens; same magnification as in b. (b) Lens pairs from 11-mo-old NrCAM−/− siblings. (c) Eye of a freshly killed 4-mo-old NrCAM mouse. (d) Weights of NrCAM+/− and NrCAM−/− littermates during postnatal development. Black line and symbols, NrCAM+/− animals; light line and symbols, NrCAM−/− animals. (e) Rotarod test. The number of times the animals fell from the rod in 3 min is indicated for a nonmoving rod and the rod rotating with 6.5 rpm. Each animal was confronted without prior rod experience, first with the nonmoving rod, and after a recovery time, with the rotating rod.
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Related In: Results  -  Collection

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fig2: NrCAM-deficient mice develop cataracts and reveal reduced body weight and motor disabilities. (a) Stages of cataract development. From left to right: 1.5-mo-old NrCAM+/− lens; NrCAM−/− littermate; both lenses from 4-mo-old NrCAM−/− mouse; 9-mo-old NrCAM−/− lens; same magnification as in b. (b) Lens pairs from 11-mo-old NrCAM−/− siblings. (c) Eye of a freshly killed 4-mo-old NrCAM mouse. (d) Weights of NrCAM+/− and NrCAM−/− littermates during postnatal development. Black line and symbols, NrCAM+/− animals; light line and symbols, NrCAM−/− animals. (e) Rotarod test. The number of times the animals fell from the rod in 3 min is indicated for a nonmoving rod and the rod rotating with 6.5 rpm. Each animal was confronted without prior rod experience, first with the nonmoving rod, and after a recovery time, with the rotating rod.
Mentions: NrCAM-deficient mice are viable and fertile. Although the gross anatomy of the nervous system appears normal, mutant mice develop a mature cataract in their lenses that becomes visible from the outside of the eye after 4 mo of age (Fig. 2 c). This cataract development was found to be progressive: 1-mo-old mice had lenses that were slightly less translucent in the nuclear region than wild-type lenses, and 4-mo-old mice already had a white opaque lens center. 9-mo-old mice had completely opaque lenses (Fig. 2 a). However, we could observe some variance in the degree of opacity and size as demonstrated by the comparison of lenses of several 11-mo-old NrCAM−/− siblings (Fig. 2 b; compare also 4-mo-old lenses in Fig 2 a). Upon piercing mutant cataract lenses with forceps, material was extruded, indicating liquefication of secondary lens fibers. After removal of the lens capsule and its adhering tissue, only the hardened interior of primary lens fibers remained, looking not transparent like in wild-type but whitish, with an irregular surface. All adult NrCAM-deficient mice examined to date had a cataract indicating a penetrance of 100%.

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