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Loss of AND-34/BCAR3 expression in mice results in rupture of the adult lens.

Near RI, Smith RS, Toselli PA, Freddo TF, Bloom AB, Vanden Borre P, Seldin DC, Lerner A - Mol. Vis. (2009)

Bottom Line: We sought to establish the effects of the loss of AND-34 expression in a mammalian organism.A small percentage of AND-34(-/-) mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber.Basal levels of p130Cas phosphorylation were higher in AND-34(+/+) than in AND-34(-/-) lens epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Boston Medical Center, Boston, MA 2118, USA.

ABSTRACT

Purpose: AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. Expression of AND-34 regulates epithelial cell growth pattern, motility, and growth factor dependence. We sought to establish the effects of the loss of AND-34 expression in a mammalian organism.

Methods: AND-34(-/-) mice were generated by homologous recombination. Histopathology, in situ hybridization, and western blotting were performed on murine tissues.

Results: Western analyses confirmed total loss of expression in AND-34(-/-) splenic lymphocytes. Mice lacking AND-34 are fertile and have normal longevity. While AND-34 is widely expressed in wild type mice, histologic analysis of multiple organs in AND-34(-/-) mice is unremarkable and analyses of lymphocyte development show no overt changes. A small percentage of AND-34(-/-) mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber. Following initial vacuolization and liquefaction of the lens cortex first observed at postnatal day three, posterior lens rupture occurs in all AND-34(-/-) mice, beginning as early as three weeks and seen in all mice at three months. Western blot analysis and in situ hybridization confirmed the presence of AND-34 RNA and protein in lens epithelial cells, particularly at the lens equator. Prior data link AND-34 expression to the activation of Akt signaling. While Akt Ser 473 phosphorylation was readily detectable in AND-34(+/+) lens epithelial cells, it was markedly reduced in the AND-34(-/-) lens epithelium. Basal levels of p130Cas phosphorylation were higher in AND-34(+/+) than in AND-34(-/-) lens epithelium.

Conclusions: These results demonstrate the loss of AND-34 dysregulates focal adhesion complex signaling in lens epithelial cells and suggest that AND-34-mediated signaling is required for maintenance of the structural integrity of the adult ocular lens.

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Related in: MedlinePlus

Paraffin-embedded histopathology of AND-34−/− mouse eyes. Paraffin tissue sections of four-month-old AND-34−/− eyes are compared with a four-month-old AND-34+/+ eye. Panel B shows a fragment of anterior chamber lens cortex (short arrow) in front of the iris (long arrow). Panel C shows a fragment of lens cortex (short arrow) behind the iris (long arrow). Panel D shows that the fragment of lens cortex lacks both epithelial cells and a lens capsule. The lens capsule is visible in the lens itself on the left side of this panel. In panels A and B, the loss of lens fiber material from the lens is due to artifactual shearing during the cutting of the paraffin section.
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f5: Paraffin-embedded histopathology of AND-34−/− mouse eyes. Paraffin tissue sections of four-month-old AND-34−/− eyes are compared with a four-month-old AND-34+/+ eye. Panel B shows a fragment of anterior chamber lens cortex (short arrow) in front of the iris (long arrow). Panel C shows a fragment of lens cortex (short arrow) behind the iris (long arrow). Panel D shows that the fragment of lens cortex lacks both epithelial cells and a lens capsule. The lens capsule is visible in the lens itself on the left side of this panel. In panels A and B, the loss of lens fiber material from the lens is due to artifactual shearing during the cutting of the paraffin section.

Mentions: Initial histologic studies on paraffin-embedded AND-34−/− eyes showed that the anterior chamber phenotype was due to cortical lens fragments floating in the aqueous humor (Figure 5B). Extruded cortical lens material was also seen posterior to the iris (Figure 5C). Lens capsule and lens epithelial cells were absent from the anterior chamber cortical lens fragments (Figure 5D). No extruded lens cortex or cataracts were detected in AND-34+/− or AND-34+/+ mice (Figure 5A and Figure 6A).


Loss of AND-34/BCAR3 expression in mice results in rupture of the adult lens.

Near RI, Smith RS, Toselli PA, Freddo TF, Bloom AB, Vanden Borre P, Seldin DC, Lerner A - Mol. Vis. (2009)

Paraffin-embedded histopathology of AND-34−/− mouse eyes. Paraffin tissue sections of four-month-old AND-34−/− eyes are compared with a four-month-old AND-34+/+ eye. Panel B shows a fragment of anterior chamber lens cortex (short arrow) in front of the iris (long arrow). Panel C shows a fragment of lens cortex (short arrow) behind the iris (long arrow). Panel D shows that the fragment of lens cortex lacks both epithelial cells and a lens capsule. The lens capsule is visible in the lens itself on the left side of this panel. In panels A and B, the loss of lens fiber material from the lens is due to artifactual shearing during the cutting of the paraffin section.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666772&req=5

f5: Paraffin-embedded histopathology of AND-34−/− mouse eyes. Paraffin tissue sections of four-month-old AND-34−/− eyes are compared with a four-month-old AND-34+/+ eye. Panel B shows a fragment of anterior chamber lens cortex (short arrow) in front of the iris (long arrow). Panel C shows a fragment of lens cortex (short arrow) behind the iris (long arrow). Panel D shows that the fragment of lens cortex lacks both epithelial cells and a lens capsule. The lens capsule is visible in the lens itself on the left side of this panel. In panels A and B, the loss of lens fiber material from the lens is due to artifactual shearing during the cutting of the paraffin section.
Mentions: Initial histologic studies on paraffin-embedded AND-34−/− eyes showed that the anterior chamber phenotype was due to cortical lens fragments floating in the aqueous humor (Figure 5B). Extruded cortical lens material was also seen posterior to the iris (Figure 5C). Lens capsule and lens epithelial cells were absent from the anterior chamber cortical lens fragments (Figure 5D). No extruded lens cortex or cataracts were detected in AND-34+/− or AND-34+/+ mice (Figure 5A and Figure 6A).

Bottom Line: We sought to establish the effects of the loss of AND-34 expression in a mammalian organism.A small percentage of AND-34(-/-) mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber.Basal levels of p130Cas phosphorylation were higher in AND-34(+/+) than in AND-34(-/-) lens epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Boston Medical Center, Boston, MA 2118, USA.

ABSTRACT

Purpose: AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. Expression of AND-34 regulates epithelial cell growth pattern, motility, and growth factor dependence. We sought to establish the effects of the loss of AND-34 expression in a mammalian organism.

Methods: AND-34(-/-) mice were generated by homologous recombination. Histopathology, in situ hybridization, and western blotting were performed on murine tissues.

Results: Western analyses confirmed total loss of expression in AND-34(-/-) splenic lymphocytes. Mice lacking AND-34 are fertile and have normal longevity. While AND-34 is widely expressed in wild type mice, histologic analysis of multiple organs in AND-34(-/-) mice is unremarkable and analyses of lymphocyte development show no overt changes. A small percentage of AND-34(-/-) mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber. Following initial vacuolization and liquefaction of the lens cortex first observed at postnatal day three, posterior lens rupture occurs in all AND-34(-/-) mice, beginning as early as three weeks and seen in all mice at three months. Western blot analysis and in situ hybridization confirmed the presence of AND-34 RNA and protein in lens epithelial cells, particularly at the lens equator. Prior data link AND-34 expression to the activation of Akt signaling. While Akt Ser 473 phosphorylation was readily detectable in AND-34(+/+) lens epithelial cells, it was markedly reduced in the AND-34(-/-) lens epithelium. Basal levels of p130Cas phosphorylation were higher in AND-34(+/+) than in AND-34(-/-) lens epithelium.

Conclusions: These results demonstrate the loss of AND-34 dysregulates focal adhesion complex signaling in lens epithelial cells and suggest that AND-34-mediated signaling is required for maintenance of the structural integrity of the adult ocular lens.

Show MeSH
Related in: MedlinePlus