Imprinting of the insulin-like growth factor II gene (IGF-II) is conserved in human, rat, and mouse. In human liver and chondrocytes, IGF-II transcripts from promoter hP1 are always derived from both parental alleles, while transcripts from promoters hP2-hP4 are from one parental allele. To examine the promoter-specific imprinting pattern of mouse IGF-II, we examined IGF-II expression in F1 generation mice derived from crossing M. spretus with M. musculus using a novel BsaA1 polymorphism in mouse IGF-II exon 6. There was maintenance of maternal IGF-II imprinting in all non-central nervous system (CNS) tissues in the F1 generation animals. However, there was biallelic expression of the IGF-II gene in CNS. Allelic expression of each IGF-II promoter transcript was examined by full-length cDNA amplification with promoter-specific primers. In every tissue in which IGF-II was imprinted, IGF-II transcripts were derived from paternal promoters mP1-mP3, while the maternal allele was suppressed. In the CNS, however, promoters mP1-mP3 of the imprinted maternal allele became activated, leading to the biallelic expression of IGF-II. Moreover, the expression of IGF-II from each parental allele differed in various CNS regions. In leptomeninges, mP1-mP3 drive IGF-II expression predominantly from the paternal allele, while in some CNS regions, the promoter transcripts were primarily from the maternal allele. The coordinate regulation of mouse IGF-II promoters suggests the presence of an upstream imprinting complex controlling IGF-II imprinting.(ABSTRACT TRUNCATED AT 250 WORDS)