EXPRESSION AND ACTIVITY OF L-MYC IN NORMAL MOUSE DEVELOPMENT

To determine the role of L-Myc in normal mammalian development and its functional relationship to other members of the Myc family, we determ ined the normal patterns of L-myc gene expression in the developing mo use by RNA in situ hybridization and assessed the phenotypic impact of L-Myc deficiency produced through standard gene targeting methodology , L-myc transcripts were detected in the developing kidney and lung as well as in both the proliferative and the differentiative zones of th e brain and neural tube, Despite significant expression of L-myc in de veloping mouse tissues, homozygous null L-myc mice were found to be vi able, reproductively competent, and represented in expected frequencie s from heterozygous matings, A detailed histological survey of embryon ic and adult tissues, characterization of an embryonic neuronal marker , and measurement of cellular proliferation in situ did not reveal any congenital abnormalities. The lack of an apparent phenotype associate d with L-Myc deficiency indicates that L-Myc is dispensable for gross morphological development and argues against a unique role for L-Myc i n early central nervous system development as had been previously sugg ested, Although overlapping expression patterns among myc family membe rs raise the possibility of complementation of L-Myc deficiency by oth er Myc oncoproteins, compensatory changes in the levels of c- and/or N -myc transcripts were not detected in homozygous null L-myc mice.