The transcripts of zeta-crystallin, a lens protein related to the alcohol dehydrogenase family, are altered in a guinea-pig hereditary cataract.
Zeta-Crystallin, a major component of the guinea-pig lens proteins, is distantly related to the enzymes of the zinc-containing alcohol dehydrogenase family (ADH). Analysis of the structural similarities between zeta-crystallin and ADH reveals that while characteristics important in maintaining the tertiary structure of the molecule appear conserved, the amino acids binding the catalytic zinc atom are absent in zeta-crystallin. Significantly, zeta-crystallin does not have ADH activity. Previous studies showed that the zeta-crystallin protein is modified in the lens of guinea-pigs affected with an autosomal dominant hereditary cataract. We have further investigated the molecular origin of the lens defect by examining the steady-state levels of zeta-crystallin transcripts in normal and mutant eyes. Our data indicate that no normal zeta-crystallin mRNA is present in the lens of the homozygous animals; instead, a cross-hybridizing lower molecular weight mRNA is detected at significantly reduced concentrations. Heterozygous lenses exhibit both mRNA species.
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
T
T
Borrás
H
H
Jörnvall
A
A
Rodokanaki
P
P
Gonzalez
I
I
Rodriguez
C
C
Hernandez-Calzadilla
D000595:Amino Acid Sequence; D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000378:metabolism; D003459:Crystallins / Q000235:genetics*; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012313:RNA / Q000032:analysis; D014158:Transcription, Genetic
D003459:Crystallins; D012313:RNA