Spatial and temporal expression patterns of the choroideremia gene in the mouse retina.

PURPOSE

Choroideremia (CHM), an X-linked retinal disease, is caused by mutations affecting the CHM gene. This gene encodes REP-1, which functions in the covalent modifications of proteins involved in vesicle trafficking. The disease affects several cell types in the retina, but it is not known which cell types contribute directly or indirectly to disease progression. A study of the expression patterns of Chm and the related gene Chml in the mouse retina was undertaken in order to address this issue.

METHODS

The expression patterns of Chm and Chml were determined by in situ hybridization. The localization of the Chm protein product, Rep-1, was determined spatially and temporally in the mouse retina by immunohistochemistry.

RESULTS

Chm and Chml mRNA were found in every major layer of the retina in adult mice. During development, Rep-1 protein localization changes from a fairly diffuse pattern during embryogenesis to a more specific pattern at the time of retinal differentiation. In adulthood, Rep-1 localizes to distinct cellular compartments in multiple retinal cell types.

CONCLUSIONS

Chm and Chml have the same broad expression profile in the mouse retina. In particular, the Chm transcript and corresponding protein are found in cell types other than those thought to be primarily affected in the human disease. These results have important implications for approaches with which to develop a relevant mouse model of choroideremia and for therapeutic strategies for this disease.