First published online September 9, 2005
Development 132, 1906e (2005)
© The Company of Biologists Limited
Closing the gap on oculodentodigital dysplasia
The human autosomal dominant disorder oculodentodigital dysplasia (ODDD) is
characterized by developmental anomalies of the limbs, teeth, face and eyes.
Mutations in the gap junction protein alpha 1 gene (GJA1), which
encodes connexin 43 (Cx43), have recently been linked to ODDD. Now, Flenniken
and colleagues describe a heterozygous mutant mouse
(Gja1Jrt/+) that exhibits many of the characteristics of
human ODDD (see p.
4375). The mutant mice have a point mutation in Gja1 that
causes a substitution of a highly conserved amino acid (G60S) in Cx43. The
researchers show that this mutant Cx43 acts in a dominant- negative manner to
disrupt gap junction assembly and function in vivo and in vitro. They also
describe the phenotype of the Cja1Jrt/+ mice in detail,
highlighting some abnormalities not normally seen in human ODDD patients but
which might cause problems as these individuals
age.
Related articles in Development:
- A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia
- Ann M. Flenniken, Lucy R. Osborne, Nicole Anderson, Nadia Ciliberti, Craig Fleming, Joanne E. I. Gittens, Xiang-Qun Gong, Lois B. Kelsey, Crystal Lounsbury, Luisa Moreno, Brian J. Nieman, Katie Peterson, Dawei Qu, Wendi Roscoe, Qing Shao, Dan Tong, Gregory I. L. Veitch, Irina Voronina, Igor Vukobradovic, Geoffrey A. Wood, Yonghong Zhu, Ralph A. Zirngibl, Jane E. Aubin, Donglin Bai, Benoit G. Bruneau, Marc Grynpas, Janet E. Henderson, R. Mark Henkelman, Colin McKerlie, John G. Sled, William L. Stanford, Dale W. Laird, Gerald M. Kidder, S. Lee Adamson, and Janet Rossant
Development 2005 132: 4375-4386.
[Abstract]
[Full Text]
