Novel human mutation and CRISPR/Cas genome-edited mice reveal the importance of C-terminal domain of MSX1 in tooth and palate development

Mitsui, Silvia Naomi; Yasue, Akihiro; Masuda, Kiyoshi; Naruto, Takuya; Minegishi, Yoshiyuki; Oyadomari, Seiichi; Noji, Sumihare; Imoto, Issei; Tanaka, Eiji

doi:10.1038/srep38398

Cited by 13 publications

(6 citation statements)

References 42 publications

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“…We summarized and analyzed the genotype–phenotype relationships of NSTA caused by MSX1 variants reported in 1996–2022 (Abid et al., 2017; Adachi et al., 2021; AlFawaz et al., 2015; Arte et al., 2013; Bergendal et al., 2011; Biedziak et al., 2022; Bonczek et al., 2018; Ceyhan et al., 2014; Chishti et al., 2006; Daw et al., 2017; De Muynck et al., 2004; Kamamoto et al., 2011; Keskin et al., 2022; Kim et al., 2006; Kimura et al., 2014; Ma et al., 2020; Mitsui et al., 2016; Mostowska et al., 2006, 2012; Mu et al., 2013; Şahan & Akan, 2021; Tatematsu et al., 2015; Vastardis et al., 1996; Wong et al., 2014; Xin et al., 2018; Xuan et al., 2008; Xue et al., 2016; Yamaguchi et al., 2014; Yang et al., 2020; Yue et al., 2022; Zheng et al., 2021). In brief, we identified 46 patients with 44 MSX1 variants, including the patients in this study (Table S1).…”

Section: Resultsmentioning

confidence: 99%

Characterization of novel MSX1 variants causally associated with non‐syndromic oligodontia in Chinese families

Zhao,

Ren,

Meng

et al. 2023

Molec Gen & Gen Med

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BackgroundMSX1 (OMIM #142983) is crucial to normal dental development, and variants in MSX1 are associated with dental anomalies. The objective of this study was to characterize the pathogenicity of novel MSX1 variants in Chinese families with non‐syndromic oligodontia (NSO).MethodsGenomic DNA was extracted from individuals representing 35 families with non‐syndromic oligodontia and was analyzed by Sanger sequencing and whole‐exome sequencing. Pathogenic variants were screened via analyses involving PolyPhen‐2, Sorting‐Intolerant from Tolerant, and MutationTaster, and conservative analysis of variants. Patterns of MSX1‐related NSO were analyzed. MSX1 structural changes suggested functional consequences in vitro.ResultsThree previously unreported MSX1 heterozygous variants were identified: one insertion variant (c.576_577insTAG; p.Gln193*) and two missense variants (c. 871T>C; p.Tyr291His and c. 644A>C; p.Gln215Pro). Immunofluorescence analysis revealed abnormal subcellular localization of the p.Gln193* MSX1 variant. In addition, we found that these MSX1 variants likely lead to the loss of second premolars.ConclusionThree novel MSX1 variants were identified in Chinese Han families with NSO, expanding the MSX1 variant spectrum and presenting a genetic origin for the pathogenesis detected in patients and their families.

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Section: Resultsmentioning

confidence: 99%

Characterization of novel MSX1 variants causally associated with non‐syndromic oligodontia in Chinese families

Zhao,

Ren,

Meng

et al. 2023

Molec Gen & Gen Med

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“…For example, CRISPR technology has been used to reveal the importance of C-terminal domain of Msx1 gene in tooth and palate development. Mitsui et al (2016) targeted Msx1 in mice with CRISPR system in homozygous mice exhibited agenesis of lower incisors with or without cleft palate (Mitsui et al, 2016). In the same context, MSX1 homeodomain also has been identified in non-syndromic tooth agenesis predominantly affecting premolars and third molars (Vastardis et al, 1996).…”

Section: Crispr Technologymentioning

confidence: 99%

How orthodontic research can be enriched and advanced by the novel and promising evolutions in biomedicine

2021

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Recent advances in developmental, molecular and cellular biology as well as biomedical technologies show a promising future for crossing the gap between biomedical basic sciences and clinical orthodontics. Orthodontic research shall utilise the advances and technologies in biomedical fields including genomics, molecular biology, bioinformatics and developmental biology. This review provides an update on the novel and promising evolutions in biomedicine and highlights their current and likely future implementation to orthodontic practice. Biotechnological opportunities in orthodontics and dentofacial orthopaedics are presented with regards to CRISPR technology, multi-omics sequencing, gene therapy, stem cells and regenerative medicine. Future orthodontic advances in terms of translational research are also discussed. Given the breadth of applications and the great number of questions that the presently available novel biomedical tools and techniques raise, their use may provide orthodontic research in the future with a great potential in understanding the aetiology of dentofacial deformities and malocclusions as well as in improving the practice of this clinical specialty.

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“…Through in vitro CRISPR-targeted disruptions, smchd1 and kinesin-1 genes were found to be critical in craniofacial cartilage formation (Shaw et al 2017; Santos-Ledo et al 2017). Knockout mice generated by CRISPR/Cas9 revealed the important roles of Golgb1 and Msx1 in tooth and palate development (Lan et al 2016; Mitsui et al 2016). CRISPR also facilitates the creations of reporter murine models (i.e., tamoxifen-inducible Pax9-CreER mice, Axin2-mTurquoise2 mice) to investigate craniofacial development (Feng et al 2016; de Roo et al 2017).…”

Section: Applications Of Genome Editing Techniques In the Oral And Crmentioning

confidence: 99%

Genome Editing: A New Horizon for Oral and Craniofacial Research

Yang

Mishina

et al. 2018

J Dent Res

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Precise and efficient genetic manipulations have enabled researchers to understand gene functions in disease and development, providing a platform to search for molecular cures. Over the past decade, the unprecedented advancement of genome editing techniques has revolutionized the biological research fields. Early genome editing strategies involved many naturally occurring nucleases, including meganucleases, zinc finger nucleases, and transcription activator-like effector-based nucleases. More recently, the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated nucleases (CRISPR/Cas) system has greatly enriched genetic manipulation methods in conducting research. Those nucleases generate double-strand breaks in the target gene sequences and then utilize DNA repair mechanisms to permit precise yet versatile genetic manipulations. The oral and craniofacial field harbors a plethora of diseases and developmental defects that require genetic models that can exploit these genome editing techniques. This review provides an overview of the genome editing techniques, particularly the CRISPR/Cas9 technique, for the oral and craniofacial research community. We also discuss the details about the emerging applications of genome editing in oral and craniofacial biology.

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Novel human mutation and CRISPR/Cas genome-edited mice reveal the importance of C-terminal domain of MSX1 in tooth and palate development

Cited by 13 publications

References 42 publications

Characterization of novel MSX1 variants causally associated with non‐syndromic oligodontia in Chinese families

Characterization of novel MSX1 variants causally associated with non‐syndromic oligodontia in Chinese families

How orthodontic research can be enriched and advanced by the novel and promising evolutions in biomedicine

Genome Editing: A New Horizon for Oral and Craniofacial Research

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