Chunk #13 — Results — Kal7 is expressed in the major neuronal cell types in nucleus accumbens and dorsal striatum — Usage of promoters encoding full-length mouse Kalrn is region-specific
With the generation of mice lacking the 3'-terminal exon unique to Kal7 and ΔKal7 (Kal7KO mice) [17] and the distinctly different response of Kal7KO mice to chronic cocaine exposure [12], a detailed analysis of Kalrn promoter usage and isoform expression in Mus musculus was undertaken (Figure 2). The genes encoding rat and human Kalrn are complex, with multiple initiation exons and multiple 3'-terminal exons responsible for the tissue-specific production of transcripts encoding functionally distinct proteins [26-28]. The gene encoding mouse Kalrn is similarly large, extending over 600 kb (Figure 2). Expression of full-length isoforms of Kalrn, in which a Sec14p domain and nine spectrin-like repeats precede the first GEF domain, is governed by four promoters and their alternative initiation exons (B, C, A, and D) located 1.4 to 180 kb upstream of exon 2 [27,28] (Figure 2). The alternative initiation exons, which are separated by large introns, encode unique N-termini that are five to 38 amino acids long. Exons 2 to 5 (35 kb) encode the common Sec14p-like domain while exons 5 through 22 (150 kb) encode the nine spectrin-like
