Figure 4.

Egr3 ablation specifically in noradrenergic neurons leads to abnormal SNS development. A, DCτlZ+ transgenic mice were mated to Egr3^+/f mice to ablate Egr3 in sympathetic neurons, but not in peripheral cells such as Schwann cells and arterial endothelial cells with which sympathetic axons interact during development. B, PCR amplification of the flx (f) and cKO allele using genomic DNA isolated from DCτlZ⁺; Egr3^f/f tissues showed loxP recombination to generate the cKO allele specifically in tissues expressing DβH (SCG neurons and adrenal chromaffin cells) but not in other tissues tested. The flx allele PCR product remains detectable in the SCG and adrenal glands from DCτlZ⁺; Egr3^f/f mice since these tissues contain several cell types (glial cells, endothelial cells, fibroblasts, adrenal cortical cells, etc.) that do not express DβH and hence, do not express Cre-recombinase. As expected, no cKO PCR product was detected in any of the tissues tested from DCτlZ; Egr3^f/f mice. C, Left, Compared with DCτlZ⁺; Egr3^+/− mice (Ctl), DCτlZ⁺; Egr3^f/− (cKO) mice had bilateral ptosis similar to the ptosis that is observed in germline Egr3 KO mice, which is caused by disruption of sympathetic innervation from the SCG to the levator muscles of the eyelids. Right, Loss of Egr3 specifically in sympathetic neurons (cKO) resulted in ∼30% loss of SCG neurons, similar to the neuron loss observed in germline Egr3 KO mice, which lacked Egr3 in all tissues. *p < 0.05, N = 4 animals of each genotype analyzed.