Functional impairment of lens aquaporin in two families with dominantly inherited cataracts

Peter Francis, Jean Ju Chung, Masato Yasui, Vanita Berry, Anthony Moore, M. Keith Wyatt, Graeme Wistow, Shomi S. Bhattacharya, Peter Agre

Research output: Contribution to journalArticle

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Abstract

Opacities in the crystalline lens of eye appear with high frequency in the general population. Dominantly inherited cataracts with differing clinical features were found in two families carrying different point mutations in the gene encoding lens water channel protein AQP0 (major intrinsic protein, MIP). Families with E134G have a uni-lamellar cataract which is stable after birth, whereas families with T138R have multi-focal opacities which increase throughout life. To establish pathophysiological relevance of cataract formation, the Xenopus laevis oocyte expression system was employed to evaluate functional defects in the mutant proteins, E134G and T138R. Both substitutions cause loss of membrane water channel activity due to impaired trafficking of the mutant proteins to the oocyte plasma membrane. Although missense mutations in AQP1 and AQP2 proteins are known to result in recessive traits in vivo and in vitro, when E134G or T138R are co-expressed with wild-type AQP0 protein, the mutant proteins exhibit dominant negative behaviour. To our knowledge, these studies represent the first in vitro demonstration of functionally defective AQP0 protein from humans with congenital cataracts. Moreover, these observations predict that less severe defects in the AQP0 protein may contribute to lens opacity in patients with common, less fulminant forms of cataracts.

Original languageEnglish
Pages (from-to)2329-2334
Number of pages6
JournalHuman Molecular Genetics
Volume9
Issue number15
Publication statusPublished - 2000 Sep 22
Externally publishedYes

Fingerprint

Aquaporins
Cataract
Lenses
Mutant Proteins
Oocytes
Aquaporin 2
Aquaporin 1
Crystalline Lens
Crystallins
Xenopus laevis
Missense Mutation
Ion Channels
Point Mutation
Cell Membrane
Parturition
Population
Genes
aquaporin 0
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Francis, P., Chung, J. J., Yasui, M., Berry, V., Moore, A., Wyatt, M. K., ... Agre, P. (2000). Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. Human Molecular Genetics, 9(15), 2329-2334.

Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. / Francis, Peter; Chung, Jean Ju; Yasui, Masato; Berry, Vanita; Moore, Anthony; Wyatt, M. Keith; Wistow, Graeme; Bhattacharya, Shomi S.; Agre, Peter.

In: Human Molecular Genetics, Vol. 9, No. 15, 22.09.2000, p. 2329-2334.

Research output: Contribution to journalArticle

Francis, P, Chung, JJ, Yasui, M, Berry, V, Moore, A, Wyatt, MK, Wistow, G, Bhattacharya, SS & Agre, P 2000, 'Functional impairment of lens aquaporin in two families with dominantly inherited cataracts', Human Molecular Genetics, vol. 9, no. 15, pp. 2329-2334.
Francis P, Chung JJ, Yasui M, Berry V, Moore A, Wyatt MK et al. Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. Human Molecular Genetics. 2000 Sep 22;9(15):2329-2334.
Francis, Peter ; Chung, Jean Ju ; Yasui, Masato ; Berry, Vanita ; Moore, Anthony ; Wyatt, M. Keith ; Wistow, Graeme ; Bhattacharya, Shomi S. ; Agre, Peter. / Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. In: Human Molecular Genetics. 2000 ; Vol. 9, No. 15. pp. 2329-2334.
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