International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

I20. Mapping and Mutational Analysis of Epiregulin

Daekee Lee¹, R Scott Pearsall¹, Sanjoy Das², SK Dey², David W Threadgill^1
1Department of Genetics, University of North Carolina, Chapel Hill, NC27599-7264, USA
²Department of Molecular Physiology, Univeristy of Kansas Medical Center, Kansas City, MO, USA

Epiregulin (Ereg), a member of the epidermal growth factor (Egf) family of polypeptide growth factors, maps near two other Egf family members, amphiregulin and betacellulin, on mouse chromosome 5 and is encoded by five exons spanning 18kb. Although Ereg binds to the various Erbb receptor combinations with relatively low binding affinity, it has potent bioactivity in cells cultured in vitro. Ereg shows dual biological function by stimulating proliferation of fibroblasts, hepatocytes , smooth muscle cells, and keratinocytes and inhibiting growth of several tumor-derived epithelial cell lines. Ereg has been suggested as a local signal mediator since expression is highly restricted in the uterus of early pregnancy, placentae, and macrophages.

In order to study the function of Ereg in vivo, we used gene targeting to integrate a lacZ reporter and to produce a null allele at Ereg. Mice homozygous for the Ereg null allele show no overt developmental defects on either an outbred Swiss or inbred 129/SvEvTAC genetic background. Both male and female homozygous null mice are fertile. In addition to further characterizing the expression profile of Ereg using the integrated lacZ reporter, we are crossing these mice to other Egf family knockouts. A phenotypic characterization of the Ereg null phenotype will be presented.