Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification

Abstract Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2 −/−) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2 +/− mice (9/9 anima...

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Main Authors: Hisaka Kurita, Hiroki Kitaura, Kazuya Nishii, Tomohiko Masaka, Kazuki Ohuchi, Masatoshi Inden, Akiyoshi Kakita, Masatake Osawa, Isao Hozumi
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Molecular Brain
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Online Access:https://doi.org/10.1186/s13041-025-01240-8
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author Hisaka Kurita
Hiroki Kitaura
Kazuya Nishii
Tomohiko Masaka
Kazuki Ohuchi
Masatoshi Inden
Akiyoshi Kakita
Masatake Osawa
Isao Hozumi
author_facet Hisaka Kurita
Hiroki Kitaura
Kazuya Nishii
Tomohiko Masaka
Kazuki Ohuchi
Masatoshi Inden
Akiyoshi Kakita
Masatake Osawa
Isao Hozumi
author_sort Hisaka Kurita
collection DOAJ
description Abstract Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2 −/−) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2 +/− mice (9/9 animals) showing no obvious abnormalities, the homozygous Slc20a2 −/− mice exhibited severe calcification at 11 months of age (5/5 animals). Whilst smaller in size and number, the deposits were also detectable in 5-month-old Slc20a2 −/− mice (2/2 animals). By contrast, no obvious alterations were detectable in visceral organs, including the lung, kidney, liver, and spleen. Consistently, in PBC patients, despite the systemic mineral metabolic disturbance, calcification occurs only in a brain restricted manner. Hence, these observations suggest that our mouse model is capable of recapitulating certain aspects of human PBC etiology. In summary, our data suggested the utility of an in vivo PBC mouse model in understanding the pathological mechanisms behind brain calcification, which leads in development of novel therapeutics against PBC.
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institution Kabale University
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language English
publishDate 2025-08-01
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spelling doaj-art-8a6b6e1d4ca44b38b8c4e4503bbc1bea2025-08-24T11:57:53ZengBMCMolecular Brain1756-66062025-08-011811410.1186/s13041-025-01240-8Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcificationHisaka Kurita0Hiroki Kitaura1Kazuya Nishii2Tomohiko Masaka3Kazuki Ohuchi4Masatoshi Inden5Akiyoshi Kakita6Masatake Osawa7Isao Hozumi8Laboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical UniversityDepartment of Pathology, Brain Research Institute, Niigata UniversityLaboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical UniversityLaboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical UniversityLaboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical UniversityLaboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical UniversityDepartment of Pathology, Brain Research Institute, Niigata UniversityDepartment of Regenerative Medicine and Applied Medical Sciences, Graduate School of Medicine, Gifu UniversityLaboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical UniversityAbstract Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2 −/−) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2 +/− mice (9/9 animals) showing no obvious abnormalities, the homozygous Slc20a2 −/− mice exhibited severe calcification at 11 months of age (5/5 animals). Whilst smaller in size and number, the deposits were also detectable in 5-month-old Slc20a2 −/− mice (2/2 animals). By contrast, no obvious alterations were detectable in visceral organs, including the lung, kidney, liver, and spleen. Consistently, in PBC patients, despite the systemic mineral metabolic disturbance, calcification occurs only in a brain restricted manner. Hence, these observations suggest that our mouse model is capable of recapitulating certain aspects of human PBC etiology. In summary, our data suggested the utility of an in vivo PBC mouse model in understanding the pathological mechanisms behind brain calcification, which leads in development of novel therapeutics against PBC.https://doi.org/10.1186/s13041-025-01240-8Primary brain calcificationSLC20A2In vivo model
spellingShingle Hisaka Kurita
Hiroki Kitaura
Kazuya Nishii
Tomohiko Masaka
Kazuki Ohuchi
Masatoshi Inden
Akiyoshi Kakita
Masatake Osawa
Isao Hozumi
Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification
Molecular Brain
Primary brain calcification
SLC20A2
In vivo model
title Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification
title_full Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification
title_fullStr Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification
title_full_unstemmed Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification
title_short Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification
title_sort generation of a new slc20a2 knockout mouse line as in vivo model for primary brain calcification
topic Primary brain calcification
SLC20A2
In vivo model
url https://doi.org/10.1186/s13041-025-01240-8
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