Cloning, expression and characterization of the murine Efemp1, a gene mutated in Doyne-Honeycomb retinal dystrophy

Development of the bone and cartilage structures is one of the best-studied systems for epithelial-mesenchymal interaction as well as proliferation and differentiation. In a screen for genes differentially expressed in mice deficient for transcription factor AP-2alpha, we have identified a gene which, based on its homology to the human EFEMP-1 gene was designated Efemp1. It encodes for six repeats similar to the domain of the epidermal growth factor. Sequence comparison with EFEMP1 genes of human and rat revealed that the three proteins share a high amino acid identity (92%), suggesting a conserved function during vertebrate development. However, there is no EFEMP1ortholog annotated in sequence databases of other non-mammalian species indicating that it might have evolved in higher vertebrates only. Analysis of the murine genomic locus revealed that the gene is encoded by 11 exons, which are spread over 80 kb of distance on murine chromosome 11A4. The multidomain protein structure may indicate that Efemp1 protein interacts with extracellular matrix components and serves to connect and integrate the function of multiple partner molecules. The gene is expressed in the embryo proper starting from day 9.5 to day 18.5 of murine development. In situ analyses showed that Efemp1 is found in condensing mesenchyme, giving rise to bone and cartilage as well as in developing bone structures of the cranial and the axial skeleton. These results will help in further defining the role of Efemp1 during murine embryogenesis.