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PMID:16439475

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Citation

Morozov, V and Wawrousek, EF (2006) Caspase-dependent secondary lens fiber cell disintegration in alphaA-/alphaB-crystallin double-knockout mice. Development 133:813-21

Abstract

alphaB-crystallin has been demonstrated, in tissue culture experiments, to be a caspase 3 inhibitor; however, no animal model studies have yet been described. Here, we show that morphological abnormalities in lens secondary fiber cells of alphaA-/alphaB-crystallin gene double knockout (DKO) mice are consistent with, and probably result from, elevated DEVDase and VEIDase activities, corresponding to caspase 3 and caspase 6, respectively. Immunofluorescence microscopy revealed an increased amount of caspase 6, and the active form of caspase 3, in specific regions of the DKO lens, coincident with the site of cell disintegration. TUNEL labeling illustrated a higher level of DNA fragmentation in the secondary fiber lens cells of DKO mice, compared with wild-type mice. Using a pull-down assay, we show interaction between caspase 6 and alphaA- but not alphaB-crystallin. These studies suggest that alpha-crystallin plays a role in suppressing caspase activity, resulting in retention of lens fiber cell integrity following degradation of mitochondria and other organelles, which occurs during the apoptosis-like pathway of lens cell terminal differentiation.

Links

PubMed Online version:10.1242/dev.02262

Keywords

Animals; Apoptosis; Caspase 3; Caspase 6; Caspases/analysis; Caspases/antagonists & inhibitors; Caspases/metabolism; DNA Fragmentation; Lens, Crystalline/abnormalities; Lens, Crystalline/cytology; Lens, Crystalline/enzymology; Mice; Mice, Knockout; Mutation; Peptide Hydrolases/metabolism; alpha-Crystallin A Chain/genetics; alpha-Crystallin A Chain/metabolism; alpha-Crystallin B Chain/genetics; alpha-Crystallin B Chain/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CASP6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P24622

F

Seeded From UniProt

complete

MOUSE:CRYAA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O08738

F

Seeded From UniProt

complete

MOUSE:CRYAA

acts_upstream_of_or_within

GO:0002088: lens development in camera-type eye

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88516

P

Seeded From UniProt

complete

MOUSE:CRYAA

acts_upstream_of_or_within

GO:0002088: lens development in camera-type eye

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1858025

P

Seeded From UniProt

complete

MOUSE:CRYAA

acts_upstream_of_or_within

GO:0043154: negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88516

P

Seeded From UniProt

complete

MOUSE:CRYAA

acts_upstream_of_or_within

GO:0060561: apoptotic process involved in morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88516

P

Seeded From UniProt

complete

MOUSE:CRYAB

acts_upstream_of_or_within

GO:0043154: negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88515

P

Seeded From UniProt

complete

MOUSE:CRYAB

acts_upstream_of_or_within

GO:0002088: lens development in camera-type eye

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88515

P

Seeded From UniProt

complete

MOUSE:CRYAB

acts_upstream_of_or_within

GO:0060561: apoptotic process involved in morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88515

P

Seeded From UniProt

complete


See also

References

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