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Max-Planck-Institut für Experimentelle Medizin
Prof. Klaus-Armin Nave

NeuroD-flox conditional targeting of the NeuroD gene

The spatio-temporal expression of basic helix-loop-helix (bHLH) transcription factors in the mammalian brain has raised interest in a subfamily of drosophila atonal-related proteins, including NeuroD, which can be associated with neuronal differentiation. NeuroD is widely expressed in the developing central and peripheral nervous system (CNS and PNS) of vertebrates. In the adult CNS, sustained NeuroD mRNA expression is detected in specific brain regions including cerebellum and hippocampus, suggesting a role of NeuroD in the function of fully differentiated neurons (Schwab et al. 2000, J. Neurosci. 20, 3714-3724). NeuroD is also expressed in endocrine cells of pancreas, intestine and pituitary, where it regulates insulin, secretin and proopiomelanocortin (POMC) gene expression, respectively. Mouse mutants homozygous for an inactivated NeuroD gene suffer from severe diabetes, and die shortly after birth (Naya et al. 1997, Genes Dev. 11, 2323-2334). We have generated mice containing a conditionally targeted NeuroD allele, circumventing perinatal lethality, and allowing cell type-specific inactivation of the floxed NeuroD gene in mice (Fig. 1). By crossing these mice to Cre-expressing mice, NeuroD can be specifically inactivated in different cell types (Fig. 2).

Fig. 1: Scheme of conditional targeting strategy of the murine NeuroD gene.

Fig. 2: Northernblot analysis. By using a mouse line expressing Cre recombinase in the cerebellum, cerebellar NeuroD expression can be specifically abolished.

Detailed information in:

Cre/loxP-mediated inactivation of the bHLH transcription factor gene NeuroD/Beta2.
Sandra Goebbels, Ulli Bode, Alexander Pieper, Ursula Fünfschilling, Markus H. Schwab and Klaus-Armin Nave.
Genesis 42: 247-252 (2005) PubMed

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