60 YEARS OF POMC: The proopiomelanocortin gene: discovery, deletion and disease

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   Figure 1

   Anatomy of the POMC gene and its transcription and translation. (A) POMC is located on the short arm of human chromosome 2 in the region indicated by the vertical red line. This region is expanded in reverse orientation in (B) indicating those genes located in the vicinity of POMC. The direction of transcription for each of these genes is shown by the small horizontal arrows. Note the small size of POMC in comparison with other genes. An expanded view of POMC is shown in (C) indicating the three main exons and the two sites of transcription described in the text. The majority of transcripts start in exon 1 giving rise to the 1200 nt mRNA indicated. This RNA is translated from an initiator methionine in exon 2 to encode the POMC peptide.
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   Figure 2

   Mouse Pomc deletion strategies. (A) shows the normal 3 exon structure of Pomc. (B) Yaswen etal. (1999) used homologous recombination to replace a 9.5kb EcoRI fragment of the gene with a Pomc fragment in which the neomycin resistance gene had replaced all of exon 3. The translation product would therefore include the first 44 codons encoded on exon 2 followed by the neomycin resistance gene. Grey boxes represent the inserted homologous sequences. (C) Challis etal. (2004) used a more complex strategy in which a targeting vector included a PCR generated fragment targeting the 5' end of a 4.1kb fragment including a mutation of the authentic ATG start codon, and an insertion within the exon 3 boundaries of a tau-lacZ-PGK-neo cassette (white box), in which the PGK-neo sequences were flanked by loxP sites for possible future use in creating conditional knockouts. Grey boxes represent the inserted homologous sequences.
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   Figure 3

   POMC mutations. Representation on a cartoon of the POMC peptide of the homozygous or compound heterozygous coding region variants that have been associated with the POMC gene deficiency syndrome (OMIM #609734) in the filled black arrows. Unfilled arrows indicate the location of the heterozygous defects that have been associated with defective β-MSH processing or function. The boxed regions represent the three MSH sequences in the peptide. JP, joining peptide; CLIP, corticotrophin-like intermediate peptide; β-end, β-endorphin.

• © 2016 Society for Endocrinology