Adult-onset alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model

John P. Sundberg*, Kathleen A. Silva, Renhua Li, Gregory A. Cox, Lloyd E. King

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Alopecia areata (AA) is an autoimmune disease that targets actively growing (anagen) hair follicles in humans and other mammals. C3H/HeJ, but not C57BL/6J, mice spontaneously develop an adult-onset form of AA. A segregating population of C3HB6F2 female mice (n = 1096), generated from crossing these two strains, was used for genome-wide linkage analysis to identify AA genetic susceptibility. Previous analysis identified susceptibility intervals on chromosomes 17 (Alaa1) and 9 (Alaa2). Using additional markers in these intervals and saturation mapping purported intervals on chromosomes 8 and 15, two additional regions were identified (Alaa3 and Alaa4, respectively). Human gene association studies identified specific human leukocyte antigen intervals comparable with those (major histocompatibility complex) found in Alaa1 in the mouse. Other human studies identified genes not found in this linkage study, but these human transcription factors are directly regulated by genes within Alaa1. These results indicate the necessity of integrating both gene association and genome-wide linkage studies in both mice and humans to understand the complex nature of these and other polygenic diseases.

Original languageEnglish
Pages (from-to)294-297
Number of pages4
JournalJournal of Investigative Dermatology
Volume123
Issue number2
DOIs
StatePublished - Aug 2004
Externally publishedYes

Keywords

  • Alaa1
  • Alaa2
  • Alaa3
  • Alaa4
  • Autoimmune disease
  • H2
  • HLA
  • Mouse models

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