The future objectives of the International Mouse Phenotyping Consortium (IMPC): functional evaluation of human disease-relevant cis-regulatory elements in the mouse genome.

Authors

Naoki Kubo, Akiko Oguchi, Hiroshi Masuya, Takanori Amano, Akihiko Sakashita, Hideya Kawaji, Takeya Kasukawa, Shinya Oki, Shinya Ayabe, Toyoyuki Takada, Atsuo Ogura, Kimiko Inoue, Yasuhiro Murakawa, Masaru Tamura, Atsushi Yoshiki, Toshihiko Shiroishi

Published in

Mammalian genome : official journal of the International Mammalian Genome Society. Volume 37. Issue 1. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

The International Mouse Phenotyping Consortium (IMPC) has established a large-scale functional genomics resource by systematically generating and phenotyping knockout mouse lines, linking gene function to mammalian phenotypes. However, interpreting disease-associated non-coding variants remains particularly challenging due to their abundance, context-dependent activity, and the complexity of gene regulation. Genome-wide association studies (GWAS) have shown that many disease-associated loci map to non-coding regions. In addition, recent large-scale consortia have catalogued millions of candidate cis-regulatory elements (CREs) across mammalian genomes; however, predicting which elements contribute to disease-relevant gene regulation and organismal phenotypes remains difficult. Together, these observations highlight disease-relevant CREs as an important but still underexplored component of human disease mechanisms. In this white paper, we outline strategies to address this challenge: (i) prioritization of disease-relevant candidate CREs, (ii) genome editing in mice to functionally evaluate CREs, and (iii) the establishment of interdisciplinary working groups. By extending its activities beyond protein-coding sequences, the IMPC has a unique opportunity to define the functional and phenotypic impact of disease-relevant CREs in vivo at scale, thereby improving our understanding of how non-coding regulatory elements contribute to mammalian phenotypes and human disease.

PMID:
42498815
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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