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Kidney Week

Abstract: TH-PO806

Analysis of Mutant Human MUC1 Transgenic Mice with Mapped Transgene Suggests Systemic Manifestation of ADTKD-MUC1

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Kaimori, Jun-Ya, Osaka University Graduate School of Medicine, Suita Osaka, Japan
  • Yamamoto, Satoko, Osaka University, Suita, OSAKA-FU, Japan
  • Yoshimura, Takuji, nara medical university, Kashihara, Japan
  • Isaka, Yoshitaka, Osaka University Graduate School of Medicine, Suita Osaka, Japan

Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene mutations (ADTKD-MUC1) is an important cause of end-stage renal disease, the reported manifestations of which have been limited to within the kidneys. However, no reports about ADTKD-MUC1 transgenic model animals have been published. Almost all MUC1 mutations were previously identified in variable-number tandem repeats (VNTRs), within which sequencing is difficult. However, we previously discovered a novel MUC1 mutation before these VNTRs.


We thus developed muMUC1 tg mice using this mutated cDNA driven by mouse Muc1 promoter and examined their phenotypes. We identified the transgene integration site by targeted locus amplification.


We identified the transgene integration site by targeted locus amplification, revealing that transgene integration did not disrupt any endogenous genes. Surprisingly, mice with high mutant MUC1 protein expression showed growth retardation with massive inflammation in skin, gut, lungs, and kidneys, due to ER stress. Because of malnutrition due to gastrointestinal tracts with inflammation, almost all growth-retarded mutant animals died after weaning. Interestingly, most animals with high mutant protein were male. Our patient re-examination in response to these tg mouse data revealed that patients had interstitial pneumonia, gastrointestinal inflammation, and dermatitis with sebaceous gland inflammation with mutant protein accumulation and ER stress.


These findings show that ADTKD-MUC1 can exhibit systemic inflammatory manifestations.


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