Generation and characterization of a Gdf1 conditional null allele.

Growth differentiation factor-1 (GDF1), a TGF-beta superfamily member, participates in early embryo patterning. Later functions are implied by the Gdf1 expression in the peripheral and central nervous system. Such roles of the gene have been difficult to study, because Gdf1 null mice die during late embryogenesis. Here, we report the production of a mouse carrying a conditional Gdf1 allele, with exon 2 flanked by loxP sites. Crossing these mice with CaMKIIalpha-Cre mice resulted in Gdf1 ablation in the forebrain postnatally. Such mice displayed no behavioral changes or altered expression levels in a set of hippocampal genes examined. However, excision of the floxed Gdf1 exon caused increased expression of the remaining part of the bicistronic Uog1-Gdf1 transcript in the hippocampus. This indicates that the transcript level is regulated by a negative feedback-loop, sensing presence of either the protein or the mRNA region encoded by Gdf1 exon 2.