Doctoral Dissertations

Hsi-Hsien Lin

Date of Award

12-1997

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Sciences

Major Professor

Michael L. Mucenski

Committee Members

Dabney K. Johnson, Lisa J. Stubbs

Abstract

Of key interest in the present study is to identify genes that may be involved in hematopoiesis. Here, a mutant mouse model system, in which the fetal hematopoietic development was impaired resulting from a mutated Cmyb proto-oncogene in vivo, is utilized. The expression levels of four genes, including Gata1, Epor, Scl, and Nfe-2, were found to be downregulated in the livers of Cmyb mutant fetuses in comparison to the phenotypically normal littermates. To identify novel genes that may be involved in hematopoiesis, the differential display technique was conducted to compare the differences in mRNA expression patterns in Cmyb wild type, heterozygous, and homozygous mutant fetal livers. Differentially expressed cDNA fragments were isolated and analyzed. A total of eight putative novel genes that are differentially expressed were identified. One of these genes, designated DD7A5-7, is expressed exclusively in cells of the myeloid lineage and was characterized as a member of a receptor family consisting of seven transmembrane segments. DD7A5-7 maps to mouse chromosome 17 and was shown to be the murine homolog of human Emr1 gene. DD7A5-7 was therefore renamed Emr1. The amino acid sequence encoded by Emr1 was found to be identical to that encoded by the F4/80 gene, whose gene product is expressed specifically on the cell surface of mouse macrophages. The biological function of the Emr1/F4/80 protein was evaluated using a gene targeting approach. Emr1 null mutant mice were generated, and no histological abnormality was observed. These results indicate that the Emr1/F4/80 protein is not required for mouse embryonic or hematopoietic development.

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