Sox10-iCreER(T2) : A mouse line to inducibly trace the neural crest and oligodendrocyte lineage
Generation of the Sox10-iCreERT2 BAC-transgenic mouse line. Scheme showing the wildtype BAC used for cloning. Exon 3 of the Sox10 gene, encoding the start codon, is replaced by a targeting vector. This targeting vector comprises the 5’ and 3’ homology arm (HA), the iCre and ERT2 coding gene sequence and the neomycin-resistance box (Neo-box) flanked by Frt-sites. After homologous recombination of the targeting vector into the wildtype BAC, the Neo-box is excised by FlpE resulting in the transgenic BAC with the targeted Sox10 0Neo-box. Position of the forward (Fw) and reverse (Rev) primers for the genotyping PCR are indicated as well as the location of the southern probe.
SOX10 is a well-conserved and widely expressed transcription factor involved in the regulation of embryonic development and in the determination of cell fate. As it is expressed in neural crest cells, their derivatives and the oligodendrocyte lineage, mutations of the protein contribute to a variety of diseases like neurocristopathies, peripheral demyelinating neuropathies and melanoma. Here, we report the generation of an inducible Sox10-iCreER(T2) BAC transgenic mouse line that labels, depending on the timepoint of induction, distinct derivatives of the otic placode and the neural crest as well as cells of the oligodendrocyte lineage. Surprisingly, we could show a neural crest origin of pericytes in the brain. Besides its use for fate-mapping, the Sox10-iCreER(T2) mouse line is a powerful tool to conditionally inactivate genes in the neural crest cells, its progeny and/or the oligodendrocyte lineage in a time-dependent fashion to gain further insights into their function and contribution to diseases. © 2011 Wiley-Liss, Inc.