Sp4^tm3(Sp4)Krc

A loxP-flanked, nuclear-targeted lacZ gene, with the exon 3 splice acceptor of the mouse Sp4 gene incorporated at its 5' end and two additional transcription termination signals from SV40 at its 3' end, was inserted into the first intron, and the rat Sp4 cDNA coding region followed by a neomycin resistance cassette and the mouse Sp4 3'UTR was inserted, in-frame, into exon 2 of the endogenous gene. Expression of the rat sequence is blocked by the triple termination signal; semi-quantitative RT-PCR analysis demonstrates leaky expression of the rat transcript at ~2-5% the level of the wild-type mouse gene. The expression pattern of lacZ in heterozygous miutant mice is the same as that observed for the endogenous Sp4 transcript by in situ hybridization. Except for low level expression in the apical ectodermal ridge, lacZ expression is restricted to the embryonic nervous system; in the adult, expression is observed primarly in the hippocampus CA1 and dentate gyrus and is restricted to the hippocampal neuronal cell layers. Full Sp4 expression can be restored and the phenotype rescued by Cre recombinase excision of lacZ in the germline. (J:110135)