Genetic disruptions of O/E2 and O/E3 genes reveal involvement in olfactory receptor neuron projection.
The mammalian Olf1/EBF (O/E) family of repeated helix-loop-helix (rHLH) transcription factors has been implicated in olfactory system gene regulation, nervous system development and B-cell differentiation. Ebf (O/E1) mutant animals showed defects in B-cell lineage and brain regions where it is the only O/E family member expressed, but the olfactory epithelium appeared unaffected and olfactory marker expression was grossly normal in these animals. In order to further study the mammalian O/E proteins, we disrupted O/E2 and O/E3 genes in mouse and placed tau-lacZ and tau-GFP reporter genes under the control of the respective endogenous O/E promoters. Mice mutant for each of these genes display reduced viability and other gene-specific phenotypes. Interestingly, both O/E2 and O/E3 knockout mice as well as O/E2/O/E3 double heterozygous animals share a common phenotype: olfactory neurons (ORN) fail to project to dorsal olfactory bulb. We suggest that a decreased dose of O/E protein may alter expression of O/E target genes and underlie the ORN projection defect.
The Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 818, Baltimore, MD 21205, USA.
Song S
SS
Wang
Joseph W
JW
Lewcock
Paul
P
Feinstein
Peter
P
Mombaerts
Randall R
RR
Reed
D000818:Animals; D017930:Genes, Reporter; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D018035:Receptors, Odorant / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D018035:Receptors, Odorant; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016875:tau Proteins