N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation.
Members of the myc family of cellular oncogenes have been implicated as transcriptional regulators in pathways that govern cellular proliferation and death. In addition, N-myc and c-myc are essential for completion of murine embryonic development. However, the basis for the evolutionary conservation of myc gene family has remained unclear. To elucidate this issue, we have generated mice in which the endogenous c-myc coding sequences have been replaced with N-myc coding sequences. Strikingly, mice homozygous for this replacement mutation can survive into adulthood and reproduce. Moreover, when expressed from the c-myc locus, N-myc is similarly regulated and functionally complementary to c-myc in the context of various cellular growth and differentiation processes. Therefore, the myc gene family must have evolved, to a large extent, to facilitate differential patterns of expression.
Malynn
B A
BA
The Center for Blood Research, Boston, Massachusetts 02115 USA.
de Alboran
I M
IM
O'Hagan
R C
RC
Bronson
R
R
Davidson
L
L
DePinho
R A
RA
Alt
F W
FW
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D001853:Bone Marrow / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003208:Concanavalin A / Q000378:metabolism; D005091:Exons; D005434:Flow Cytometry; D016259:Genes, myc / Q000235:genetics* / Q000502:physiology*; D005838:Genotype; D008070:Lipopolysaccharides / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D051379:Mice / Q000196:embryology*; D008822:Mice, Transgenic; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism; D016296:Mutagenesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D017252:CD3 Complex; D008070:Lipopolysaccharides; D016271:Proto-Oncogene Proteins c-myc; D003208:Concanavalin A