Genetic background influences cataractogenesis, but not lens growth deficiency, in Cx50-knockout mice.
OBJECTIVE
Deletion of connexin (Cx)50 produces microphthalmia with nuclear cataracts. To determine whether these two traits are influenced by genetic background and are dependent on each other, mice carrying the Cx50 deletion in two different strains were generated, and the growth defect and severity of cataracts were analyzed.


METHODS
Cx50-knockout mice were generated in the 129S6 strain, and back-crossed into the C57BL/6J genetic background. To analyze the influence of genetic background on the observed phenotype, postnatal lens growth, lens clarity, lens histology and crystallin solubility were determined and compared between the two strains of Cx50-knockout mice.


RESULTS
The growth deficiency persisted, regardless of genetic background, but genetic modifiers that differentially altered the solubility of crystallin proteins influenced the severity of cataracts. Expression levels of Cx46 were similar in all animals, regardless of genetic background, indicating that the differences were not due to a compensatory upregulation of Cx46.


CONCLUSIONS
Taken together, these data indicate that the two components of the Cx50 phenotype are independent of each other and that cataractogenesis is under the influence of an unidentified genetic modifier.
Gerido
Dwan A
DA
Department of Physiology and Biophysics, State University of New York, Stony Brook, New York 11794-8661, USA.
Sellitto
Caterina
C
Li
Leping
L
White
Thomas W
TW
D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017630:Connexins / Q000378:metabolism / Q000502:physiology*; D003433:Crosses, Genetic; D003459:Crystallins / Q000378:metabolism; D005136:Eye Proteins / Q000502:physiology*; D007908:Lens, Crystalline / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008850:Microphthalmos / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D000099264:Connexin 50
D017630:Connexins; D003459:Crystallins; D005136:Eye Proteins; D000099264:Connexin 50; C082917:GJA3 protein, human