Analysis of the desmoplakin gene reveals striking conservation with other members of the plakin family of cytolinkers

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Abstract
Members of the plakin family of cytolinker proteins integrate filaments into cellula networks and anchor these networks to the plasma membrane. Their importance is supported by the existence of cell and tissue fragility disorders caused by mutations in certain family members. In this study, the human gene encoding desmoplakin (DSP) was characterized and its structure compared with the related family members: plectin, bullous pemphigoid antigen 1 (BPAG1), envoplakin (EVPL) and periplakin (PPL). Sequence analysis of genomic clones was carried out in combination with a PCR‐based strategy to define intron‐exon border. DSP was mapped using the GB4 radiation hybrid mapping panel to the interval between markers D6S296 and AFM043Xf2, correponding to cytogenetic band 6p24. In addition, the murine gene (DSP) was mapped to mouse chromosome 13 by interspecific backcross mapping. DSP encompasses 45 kb organized into 24 exons and 23 introns, and the pattern of intron‐exon borders bears a striking resemblance to other member of the plakin family. Notable features include the fact that a single large exon encodes the entire C‐termius of each gene. In contrast, the N‐termini comprise numerous smaller exons with conservation of many genses will facilitate their further evaluation as targets of genetic disorders and provide insights into the evolutionary relationships among molecules in this emerging gene family.