An 8.5 kb 5! flanking genomic fragment of the alpha subunit of the calcium/calmodulin-dependent protein kinase II gene (CaMKIIα) has been shown to confer brain specific expression on a variety of transgenes in the mouse, including Cre recombinase (Mansuy et al., 1998; Mayford et al., 1995; Tsien et al., 1996). The pattern and level of expression of these transgenes varies considerably between different lines and, in many cases, high levels of expression are confined to the hippocampus. We have used the CaMKIIα promoter to generate additional Cre transgenic lines expressing in different regions of the developing and adult mouse brain. These transgenic lines should complement existing brain-specific Cre transgenic lines for use in Cre/loxP conditional mutagenesis strategies (Sauer, 1998). The CaMKIIα gene is expressed with tissue-specificity predominantly in the adult forebrain (Benson et al., 1992; Burgin et al., 1990; Jacobs et al., 1993). This gene encodes the α-subunit of a serine-threonine protein kinase that is involved in the regulation of a diverse set of cellular processes, including synaptic plasticity (Mayford et al., 1996a; Stevens et al., 1994). In rats, expression of CaMKIIα is restricted to the forebrain, is very high in neuronal cells of the hippocampus and cortical layers, and moderate in the caudate-putamen. The endogenous gene is also developmentally regulated (Colbran, 1992). The gene is not expressed during embryogenesis and is barely detected in the first few postnatal days. Expression increases ten-fold between postnatal day 1 (P1) and P21, with a further 2.5-fold increase by P90. This significant increase during the second and third postnatal weeks coincides with the most active period of synaptogenesis in the forebrain.

We generated 13 expressing transgenic lines using a construct composed of the 8.5 kb 5! flanking CaMKIIα gene promoter fragment (Mayford et al., 1996b), a short synthetic intron to increase the amount of stable message in the cytoplasm (Choi et al., 1991), a Cre recombinase gene containing a nuclear localization sequence (Gu et al., 1994), and a poly (A) addition sequence (Fig. 1). Transgenic constructs were injected into CBA X C57BL/6J fertilized eggs, and founders were crossed with C57BL/6J mice. All transgenic lines are at least F4 in the C57BL/6J background. Cre expression was assessed by immunohistochemical staining and by using a β-ga-