Phenotypic analysis of mice carrying human-type MAFB p.Leu239Pro mutation

Maho Kanai; Hyojung Jeon; Masami Ojima; Teppei Nishino; Toshiaki Usui; Manoj Kumar Yadav; Kaushalya Kulathunga; Naoki Morito; Satoru Takahashi; Michito Hamada

doi:10.1016/j.bbrc.2019.12.033

Phenotypic analysis of mice carrying human-type MAFB p.Leu239Pro mutation

Biochem Biophys Res Commun. 2020 Mar 5;523(2):452-457. doi: 10.1016/j.bbrc.2019.12.033. Epub 2019 Dec 25.

Authors

Affiliations

¹ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
² Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
³ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
⁴ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Department of Nephrology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
⁵ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Department of Nephrology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
⁶ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan. Electronic address: satoruta@md.tsukuba.ac.jp.
⁷ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. Electronic address: hamamichi@md.tsukuba.ac.jp.

PMID: 31882119
DOI: 10.1016/j.bbrc.2019.12.033

Abstract

The transcription factor, MafB, plays important role in the differentiation and functional maintenance of various cells and tissues, such as the inner ear, kidney podocyte, parathyroid gland, pancreatic islet, and macrophages. The rare heterozygous substitution (p.Leu239Pro) of the DNA binding domain in MAFB is the cause of Focal Segmental Glomerulosclerosis associated with Duane Retraction Syndrome, which is characterized by impaired horizontal eye movement due to cranial nerve maldevelopment in humans. In this research, we generated mice carrying MafB p.Leu239Pro (Mafb^mt/mt) and retrieved their tissues for analysis. As a result, we found that the phenotype of Mafb^mt/mt mouse was similar to that of the conventional Mafb deficient mouse. This finding suggests that the Leucine residue at 239 in the DNA binding domain plays a key role in MafB function and could contribute to the diagnosis or development of treatment for patients carrying the MafB p.Leu239Pro missense variant.

Keywords: Duane retraction syndrome; Focal segmental glomerulosclerosis; MafB; p.Leu239Pro.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Binding Sites
DNA / metabolism
Ear / embryology
Ear / pathology*
Humans
Kidney / embryology
Kidney / pathology*
MafB Transcription Factor / genetics*
MafB Transcription Factor / metabolism*
Mice, Knockout
Mice, Mutant Strains
Mutation*
Mutation, Missense
Pancreas / pathology
Parathyroid Hormone / metabolism
Phenotype

Substances

MAFB protein, human
MafB Transcription Factor
Mafb protein, mouse
Parathyroid Hormone
DNA