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B-Crystallin in Lens Development and Muscle Integrity: A Gene Knockout Approach
1 From the National Eye Institute and the 3 Pathology Section, Office of Research Services, National Institutes of Health, Bethesda, Maryland; the 5 Anatomy Department, University of Erlangen-Nürnberg, Germany; and the 6 Eye Research Institute, Oakland University, Rochester, Michigan.
PURPOSE. To study the role of 
B-crystallin (B) in the developing lens and
its importance in lens structure and function.
METHODS. Gene targeting in embryonic stem cells was used to generate mouse lines
in which the B gene and its protein product were absent. Gene
structure and expression were characterized by genomic Southern blot,
immunoblot, and Northern blot analyses, and two-dimensional gel
electrophoresis. The gene knockout mice were screened for cataract with
slit lamp biomicroscopy, and dissected lenses were examined with
dark-field microscopy. Lenses and other tissues were analyzed by
standard histology and immunohistochemistry. Chaperone activity was
determined by heating lens homogenate supernatants and measuring
absorbance changes.
RESULTS. In an unexpected result, lenses in the B gene knockout mice
developed normally and were remarkably similar to wild-type mouse
lenses. All the other crystallins were present. The thermal stability
of a lens homogenate supernatant was mildly compromised, and when
oxidatively stressed in vivo with hyperbaric oxygen, the knockout
lenses reacted similarly to wild type. In targeting the B gene, the
adjacent HSPB2 gene, which is not expressed in
the lens, was also disrupted. Loss of B and/or HSPB2 function leads
to degeneration of some skeletal muscles.
CONCLUSIONS. B is not essential for normal development of a transparent lens in
the mouse, and therefore is more dispensable to the lens than the
closely related A-crystallin. It may play a small role in
maintaining transparency throughout life. B and/or the closely
related HSPB2 is required to maintain muscle cell integrity in some
skeletal muscles.
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