Characterization of the linked ovine insulin and insulin-like growth factor-II genes.

The ovine insulin-like growth factor-II (oIGF-II) gene is comprised of 9 exons that span approximately 25 kb. Approximately 750 nucleotides upstream of oIGF-II exon 1 are the three exons of the ovine insulin gene that are transcribed in the same direction as oIGF-II. The genomic organization and expression of the oIGF-II gene is similar to that of the human IGF-II gene. Four putative promoters direct the transcription of six 5' noncoding exons (1, 3, 4, 5, 6, and 7), which are alternatively spliced to the shared exons 8, 9, and 10. An ovine exon comparable to human exon 2 has not been identified. Multiple transcription initiation sites were identified for exons 1 and 6 by primer extension analysis. Using a reverse transcriptase polymerase chain reaction (RT-PCR) assay, exon 1 and 3 transcripts were shown to be expressed in adult but not fetal liver. In addition, a novel transcript, which contained exon 1 spliced directly to exon 8, was detected in adult liver. Exon 4 transcripts were not detected in either fetal or adult liver, whereas exon 6 and 7 transcripts were detected in both fetal and adult liver. Exon 5 transcripts were also expressed in both fetal and adult liver, which is in contrast to the tumor cell-specific expression of human exon 5. Like the human and rodent genes, the regulation of expression of the oIGF-II gene is under complex control.