A5043160197- Developmental Biology and Gene Regulation
- CRISPR and Genetic Engineering
- Tendon Structure and Treatment
- MicroRNA in disease regulation
- Ubiquitin and proteasome pathways
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- Pluripotent Stem Cells Research
- TGF-β signaling in diseases
- Animal Genetics and Reproduction
- Muscle Physiology and Disorders
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- Neurogenetic and Muscular Disorders Research
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Mesenchymal stem cell research
- Shoulder Injury and Treatment
- Tissue Engineering and Regenerative Medicine
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
Meiji University
2017-2025
National Center For Child Health and Development
2014-2024
Health and Human Development (2HD) Research Network
2020
The University of Tokyo
1993-2015
University of Padua
2007-2012
Toyonaka Municipal Hospital
2006
Tokyo University of Science
2002
Introducing a point mutation is fundamental method used to demonstrate the roles of particular nucleotides or amino acids in genetic elements proteins and widely vitro experiments based on cultured cells exogenously provided DNA. However, vivo application this approach by modifying genomic loci uncommon, partly due its technical temporal demands. This leaves many findings un-validated under conditions. We herein applied CRISPR/Cas9 system generate mice with mutations their genomes, which led...
From 1999 to 2003, 34 patients with unstable distal clavicular fractures (Neer Type 2) had surgery using the acromioclavicular titanium hook plate. To investigate reliability of plate fixation and effects plates in subacromial space, we retrospectively reviewed clinical results for pain, shoulder function, range motion, radiographic results. The Japanese Orthopaedic Association scores disorders indicated good (mean, 98.3 points). All bony union. Complications included displacement one...
ABSTRACT Mohawk homeobox (MKX) has been demonstrated as a tendon/ligament specific transcription factor. The aim of this study was to investigate the role MKX in ligament/tenogenic differentiation bone marrow derived mesenchymal stem cells (BMMSCs). Human BMMSCs were treated with 50 ng/ml BMP‐12 or transduced scleraxis (SCX) adenoviral vector. Gene expression analysis performed by quantitative reverse transcribed polymerase chain reaction (qRT‐PCR). Rat seeded collagen scaffold and...
The WW domain-containing protein 2 (Wwp2) gene, the host gene of miR-140, codes for Wwp2 protein, which is an HECT-type E3 ubiquitin ligases abundantly expressed in articular cartilage. However, its function remains unclear. Here, we show that mice lacking and enzyme inactivated (Wwp2-C838A) exhibit aggravated spontaneous surgically induced osteoarthritis (OA). Consistent with this phenotype, WWP2 expression level downregulated human OA We also identify Runx2 as a substrate Adamts5 target...
Abstract The main pathogenesis of intervertebral disc (IVD) herniation involves disruption the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and resulting prolapse nucleus pulposus. Owing to avascular nature IVD lack understanding mechanisms that maintain IVD, current therapies do not lead tissue regeneration. Here we show homeobox protein Mohawk (Mkx) is a key transcription factor regulates AF development, maintenance Mkx mainly expressed in outer (OAF) humans mice....
Recently developed transcription activator-like effector nuclease (TALEN) technology has enabled the creation of knockout mice, even for genes on Y chromosome. In this study, we generated a mouse Sry, sex-determining gene chromosome, using microinjection TALEN RNA into pronuclear stage oocytes. As expected, had female external and internal genitalia, level blood testosterone sexually dimorphic nucleus in brain. The exhibited an estrous cycle performed copulatory behavior as females, although...
Abstract Genome editing, which introduces mutations in genes of interest using artificial DNA nucleases such as the ZFN, TALEN and CRISPR/Cas9 systems living cells, is a useful tool for generating mutant animals. Although provides advantages over two other systems, an easier vector construction high efficiency genome it raises concerns off-target effects when single guide RNA (gRNA) used. Recently, FokI-dCas9 (fCas9), fusion protein comprised inactivated form Cas9 nuclease domain FokI, has...
Complement factor B (CFB) is a crucial component for the activation of alternative pathway due to formation C3 convertase with C3b, which further produces C3b enhance overall complement activity. Although Cfb expressed not only in immune tissues, but also reproductive tract, physiological role reproduction remains unclear. In this study, we addressed issue by producing Cfb-knockout (KO) mice and analyzing their phenotypes. Sperm function, number ovulated oocytes, litter size were normal KO...
ABSTRACT Proper connections between cartilaginous and muscular primordia through tendinous/ligamentous are essential for musculoskeletal integration. Herein, we report a novel double-reporter mouse model investigating this process via fluorescently visualising scleraxis (Scx) SRY-box containing gene 9 (Sox9) expression. We generated ScxTomato transgenic mice crossed them with Sox9EGFP knock-in to obtain ScxTomato;Sox9EGFP mice. Deep imaging of optically cleared embryos at E13.5 E16.5...
Abstract SRY (sex-determining region Y)-box 9 (SOX9) is a transcription factor regulating both chondrogenesis and sex determination. Among vertebrates, SOX9’s functions in are well conserved, while they vary To investigate the conservation of regulatory gonad development among species, we performed chromatin immunoprecipitation sequencing (ChIP-seq) using developing limb buds male gonads from embryos two mouse chicken. In chicken, SOX9 bound to intronic distal regions genes more frequently...
NR5A1 is the key regulator of adrenal and gonadal development in both humans mice. Recently, a missense substitution human NR5A1, p.R92W, was shown to underlie dysgenesis genetic males testicular formation females. Here, we investigated phenotypic effects p.R92W mutation on murine development. Mice carrying manifested similar but milder phenotype than that previously described Nr5a1 knockout Importantly, mutation-positive XX mice showed no signs masculinization. These results, together with...
Movement of the vertebrate body is supported by connection muscle, tendon and bone. Each skeletal muscle in has a unique shape attachment site; however, mechanism that ensures reproducible patterning incompletely understood. In this study, we conducted targeted cell ablation using scleraxis (Scx)-Cre to examine role Scx-lineage cells morphogenesis mouse embryos. We found bundle shapes sites were significantly altered embryos with ablation. Muscles forelimb showed impaired separation limb...
The Spemann organizer stands out from other signaling centers of the embryo because its broad patterning effects. It defines development along anteroposterior and dorsoventral axes vertebrate body, mainly by secreting antagonists growth factors. Qualitative models proposed more than a decade ago explain organizer’s region-specific inductions (i.e., head trunk) as result different combinations antagonists. For example, induction is mediated extracellular inhibition Wnt, BMP, Nodal ligands....