老化・疾患生体制御学

    研究内容

    超高齢社会を迎え、老人性疾患の病態理解への必要性が急速に高まっています。その中で、私たちは、生体の老化と疾患の関連性を、細胞外環境に着目して研究を進めています。

    生体の機能維持には、細胞のみならず、細胞を取り囲む細胞外環境が形態保持や受容体としての役割を果たすなど、細胞と細胞外環境の相互作用が重要であることがわかっています。これらを踏まえ、本研究室では、高齢者特有の身体的、生理的特徴を動物モデル、細胞モデルを使って、形態学、分子生物学、細胞生物学的に解析することで、老人性疾患の診断法の開発および新規治療法の立案を行うことを目指します。

    また、細胞外マトリックスを介した臓器連関についても興味をもっており、単一診療科に限らず、神経内科、整形外科、循環器内科、眼科といった幅広い診療科にわたる領域を横断的に解析できることも特徴です。脳認知機能、運動器学を履修し、健康長寿を目指す最先端医科学を遂行できる人材育成を目指し、大学院生の受け入れを行っています。

    (1)脳の機能と老化における細胞外マトリックスのバイオロジー

    ① 脳の発達と糖鎖

    生後発達期の皮質における神経細胞のネットワーク形成が障害されると、さまざまな精神神経の障害を引き起こします。その病因解明はまだ十分ではありません。本研究室では、神経細胞とグリア細胞の発達過程、さらには、発達期における細胞と細胞外マトリックスのコミュニケーションにおいて糖鎖が果たす役割に関心を持っています。

    ② 神経新生と老化

    成人の脳では、神経幹細胞は神経新生領域に存在し、領域のニッチ環境が重要な役割をにないます。新しいニューロンを生み出す能力は、老化により影響を受けることが推測されますが、その原因はまだ十分解明されていません。本研究室では、神経新生において細胞外マトリックスの糖鎖が果たす役割を探索し、加齢による糖鎖修飾の変化が神経幹細胞に与える影響を調査します。

    ③ 脱細胞化脳組織を使った3次元培養の試み

    細胞外マトリックスの生体での機能を解析するため、脱細胞化脳組織を使った、より生体組織に近いマトリックス構造を維持した“3次元細胞培養”を用いた解析を行っています。これにより、従来の“2次元細胞培養”では不可能だった複雑な構造の細胞外マトリックスを用いて研究することができます。

    (2)運動器の疾患と老化の研究

    ① 神経筋疾患について

    運動による骨格筋へのメカニカルストレスは、筋萎縮の防止や機能維持に必須です。一方で、筋ジストロフィー症を代表とする疾患筋では、メカニカルストレスに対する脆弱性が筋崩壊の原因となることが知られています。しかし、どの程度のメカニカルストレスが過剰な負荷として病的機序を引き起こすのか、また変動する外的刺激に対しどのように骨格筋は適応しているのかなどの、メカニカルストレスに関わる詳細なメカニズムやその適正法は未明です。本研究室では、骨格筋における細胞外マトリックスのバイオロジーを解明する立場から、この課題の究明に取り組んでいます。また、希少性疾患であるシュワルツヤンペル症候群の研究を通じ、細胞外マトリックス異常をもたらす遺伝性筋疾患の新たな治療解明など難病研究への貢献を目指しています。

    ② 運動による老化防止効果について

    運動は、肥満や糖尿病などの代謝性疾患の改善のみならず、認知症やパーキンソン病などの加齢性疾患や老化そのものの防止に役立つことが報告されています。私たちは、骨格筋と他臓器の連関機構に着目し、老化に対する運動効果の詳細を解明するとともに予防医学への応用を目指しています。近年、ロコモティブシンドローム、フレイル、サルコペニアといった筋量や身体活動量の低下がQOLを著しく低下させることも広く認識されるようになり、AI技術も活用したビックデータ解析による社会還元にも取り組んでいます。

    ③ 脱細胞化組織を使った3次元骨格筋培養の試み

    脱細胞化骨格筋組織を使用し、マトリックス構造を維持した“3次元細胞培養”を用いた解析を行っています。これにより、従来の“2次元細胞培養”では不可能だった定性定量的メカニカルストレスの付与により疾患特異的iPS細胞を使った病態研究などを進めます。

    メンバー

    メンバー

    研究生

    • 鈴木佑治

    大学院生

    • 辻裕介

    医学部生 基礎研究医養成プログラム所属

    • 6年
      秋葉星哉
    • 6年
      大野竜暉
    • 6年
      加藤可那
    • 5年
      田中貴大
    • 5年
      豊田実和子
    • 4年
      長原史奈
    • 3年
      西村陽
    • 3年
      松田ひより
    • 2年
      安部龍征
    • 2年
      村越和輝

    業績

    2020年

    Yamashita Y, Hatano T, Ogawa T, Daida K, Motoi Y, Hattori N. Steroid‐responsive parkinsonism caused by cerebral amyloid angiopathy‐related inflammation. Mov Disord Clin Pract. , 7, 329-331, 2020.

    Yamashita Y, Ogawa T, Ogaki K, Kamo H, Sukigara T, Kitahara E, Izawa N, Iwamuro H, Oyama G, Kamagata K, Hatano T, Umemura A, Kosaki R, Kubota M, Shimo Y, Hattori N. Neuroimaging evaluation and successful treatment by using directional deep brain stimulation and levodopa in a patient with GNAO1-associated movement disorder: A case report. J Neurol Sci., 411, 116710, 2020.

    Yamashita Y, Hatano T, Ogawa T, Daida K, Motoi Y, Hattori N.
    Steroid‐responsive parkinsonism caused by cerebral amyloid angiopathy‐related inflammation. Mov Disord Clin Pract. 2020 Feb 13
    doi: 10.1002/mdc3.12901

    2019年

    de Vega S, Kondo A, Suzuki M, Arai H, Jiapaer S, Sabit H, Nakada M, Ikeuchi T, Ishijima M, Arikawa-Hirasawa E, Yamada Y, Okada Y. Fibulin-7 is overexpressed in glioblastomas and modulates glioblastoma neovascularization through interaction with angiopoietin-1. Int J Cancer, 145, 2157-2169, 2019.

    Suzuki Y, Kerever A, Tanaka T, Higashi K, Arikawa-Hirasawa E. The Structural and Compositional Changes of Chondroitin Sulfate Chains in the Aged Mouse Hippocampus. Juntendo Medical Journal, 65, 64-70, 2019.

    Yoshimura Y, Ishijima M, Ishibashi M, Liu L, Arikawa-Hirasawa E, Machida S, Naito H, Hamada C, Kominami E. A nationwide observational study of locomotive syndrome in Japan using the ResearchKit: The Locomonitor study. J Orthop Sci., 24, 1094-1104, 2019.

    Nakamura K, Ikeuchi T, Nara K, Rhodes CS, Zhang P, Chiba Y, Kazuno S, Miura Y, Ago T, Arikawa-Hirasawa E, Mukouyama YS, Yamada Y. Perlecan regulates pericyte dynamics in the maintenance and repair of the blood-brain barrier. J Cell Biol, 218, 3506-3525, 2019.

    Yamada T, Kerever A, Arikwa-Hirasawa E. Aging of Extracellular Matrix in Adult Neurogenesis. Juntendo Medical Journal, 65, 39-42, 2019.

    Tomiki Y, Saito K, Arikawa-Hirasawa E, Mita T, Shimizu T, Suzuki T, Ohnuma T, Ohtomo Y, Nagaoka I. Club Activities of Medical Students at Juntendo University – Changes of Membership over the 30-year Heisei Era. Juntendo Medical Journal, 65, 172-178, 2019.

    Kamo H, Hatano T, Kanai K, Aoki N, Kamiyama D, Yokoyama K, Takanashi M, Yamashita Y, Shimo Y, Hattori N. Pembrolizumab-related systemic myositis involving ocular and hindneck muscles resembling myasthenic gravis: a case report. BMC Neurol , 19, 184, 2019.

    2018年

    Nakazawa T N, Fujiwara N, Miyahara K, Nakada S, Arikawa-Hirasawa E, Akazawa C, Urao M, Yamataka A. The effect of laminin-1 on enteric neural crest-derived cell migration in the Hirschsprung’s disease mouse model. Pediatr Surg Int. , 17, 138-144, 2018.

    Irie R, Kamagata K, Kerever A, Ueda R, Yokosawa S, Otake Y, Ochi H, Yoshizawa H, Hayashi A, Tagawa K, Okazawa H, Takahashi K, Sato K, Hori M, Arikawa-Hirasawa E, Aoki S. The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging. Magn Reson Med Sci, 17, 138-144, 2018

    Yamashita Y, Nakada S, Yoshihara T, Nara T, Furuya N, Miida T, Hattori N, Arikawa-Hirasawa E. Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with dynamic changes in adipose tissue and skeletal muscle. Sci Rep., 8, 7766, 2018.

    Ikeuchi T, de Vega S, Forcinito P, Doyle AD, Amaral J, Rodriguez IR, Arikawa-Hirasawa E, Yamada Y. Extracellular Protein Fibulin-7 and Its C-Terminal Fragment Have In Vivo Antiangiogenic Activity. Sci Rep., 8, 17654, 2018.

    2017年

    Sadatsuki R, Kaneko H, Kinoshita M, Futami I, Nonaka R, Culley KL, Otero M, Hada S, Goldring MB, Yamada Y, Kaneko K, Arikawa-Hirasawa E, Ishijima M. Perlecan is required for the chondrogenic differentiation of synovial mesenchymal cells through regulation of Sox9 gene expression. J Orthop Res., 35, 837-846, 2017.

    Sato K, Kerever A, Kamagata K, Tsuruta K, Irie R, Tagawa K, Okazawa H, Arikawa-Hirasawa E, Nitta N, Aoki I, Aoki S. Understanding microstructure of the brain by comparison of neurite orientation dispersion and density imaging (NODDI) with transparent mouse brain. Acta Radiol Open, 6, 2058460117703816, 2017.

    Fujiwara N, Nakazawa-Tanaka N, Miyahara K, Arikawa-Hirasawa E, Akazawa C, Yamataka A. Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung’s disease. Pediatr Surg Int., 34, 137-141, 2018.

    Yamada T, Kerever A, Yoshimura Y, Suzuki Y, Nonaka R, Higashi K, Toida T, Mercier F, Arikawa-Hirasawa E. Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor-2 signaling impairment in the aged neurogenic niche. J Neurochem, 142, 534-544, 2017.

    2016年

    de Vega S, Hozumi K, Suzuki N, Nonaka R, Seo E, Takeda A, Ikeuchi T, Nomizu M, Yamada Y, Arikawa-Hirasawa E. Identification of Peptides Derived from the C-terminal Domain of Fibulin-7 Active for Endothelial Cell Adhesion and Tube Formation Disruption. Biopolymers, 106, 184-195, 2016.

    Kamagata K, Kerever A, Yokosawa S, Otake Y, Ochi H, Hori M, Kamiya K, Tsuruta K, Tagawa K, Okazawa H, Aoki S, Arikawa-Hirasawa E. Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon Microscopy of Cleared Mouse Brain. Magn Reson Med Sci., 15, 416-421, 2016.

    2015年

    Nonaka R, Iesaki T, de Vega S, Daida H, Okada T, Sasaki T, and Arikawa-Hirasawa E. Perlecan deficiency causes endothelial dysfunction by reducing the expression of endothelial nitric oxide synthase. Physiol Rep., 3, e12272, 2015.

    Kerever A, Kamagata K, Yokosawa S, Otake Y, Ochi H, Yamada T, Hori M, Kamiya K, Nishikori A, Aoki S, Arikawa-Hirasawa E. See-through Brains and Diffusion Tensor MRI Clarified Fiber Connections. Magnetic Resonance in Medical Sciences, 14, 159-162, 2015.

    Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, Masuda A, Goto T, Adachi M, Osaka H, Nonaka R, Arikawa-Hirasawa E, Ohno K. A missense mutation in domain III in HSPG2 in Schwartz–Jampel syndrome compromises secretion of perlecan into the extracellular space. Neuromuscul Disord, 25, 667-671, 2015.

    Kerever A, Yamada T, Suzuki Y Mercier F, Arikawa-Hirasawa E. Fractone aging in the subventricular zone of the lateral ventricle. J Chem Neuroanat., 66-67, 52-60, 2015. 

    Ning L, Xu Z, Furuya N, Nonaka R, Yamada Y, Arikawa-Hirasawa E. Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle. Matrix Biol., 48, 263, 2015.

    2016年

    de Vega S, Hozumi K, Suzuki N, Nonaka R, Seo E, Takeda A, Ikeuchi T, Nomizu M, Yamada Y, Arikawa-Hirasawa E. Identification of Peptides Derived from the C-terminal Domain of Fibulin-7 Active for Endothelial Cell Adhesion and Tube Formation Disruption. Biopolymers, 106, 184-195, 2016.

    Kamagata K, Kerever A, Yokosawa S, Otake Y, Ochi H, Hori M, Kamiya K, Tsuruta K, Tagawa K, Okazawa H, Aoki S, Arikawa-Hirasawa E. Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon Microscopy of Cleared Mouse Brain. Magn Reson Med Sci., 15, 416-421, 2016.

    2015年

    Nonaka R, Iesaki T, de Vega S, Daida H, Okada T, Sasaki T, and Arikawa-Hirasawa E. Perlecan deficiency causes endothelial dysfunction by reducing the expression of endothelial nitric oxide synthase. Physiol Rep., 3, e12272, 2015.

    Kerever A, Kamagata K, Yokosawa S, Otake Y, Ochi H, Yamada T, Hori M, Kamiya K, Nishikori A, Aoki S, Arikawa-Hirasawa E. See-through Brains and Diffusion Tensor MRI Clarified Fiber Connections. Magnetic Resonance in Medical Sciences, 14, 159-162, 2015.

    Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, Masuda A, Goto T, Adachi M, Osaka H, Nonaka R, Arikawa-Hirasawa E, Ohno K. A missense mutation in domain III in HSPG2 in Schwartz–Jampel syndrome compromises secretion of perlecan into the extracellular space. Neuromuscul Disord, 25, 667-671, 2015.

    Kerever A, Yamada T, Suzuki Y Mercier F, Arikawa-Hirasawa E. Fractone aging in the subventricular zone of the lateral ventricle. J Chem Neuroanat., 66-67, 52-60, 2015. 

    Ning L, Xu Z, Furuya N, Nonaka R, Yamada Y, Arikawa-Hirasawa E. Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle. Matrix Biol., 48, 263, 2015.

    2014年

    Furuya N, Ikeda SI, Sato S, Soma S, Ezaki J, Trejo JA, Takeda-Ezaki M, Fujimura T, Arikawa-Hirasawa E, Tada N, Komatsu M, Tanaka K, Kominami E, Hattori N, Ueno T. PARK2/Parkin-mediated mitochondrial clearance contributes to proteasome activation during slow-twitch muscle atrophy via NFE2L1 nuclear translocation. Autophagy, 10, 631-641, 2014.

    de Vega S, Suzuki N, Nonaka R, Sasaki T, Forcinito P, Arikawa-Hirasawa E, Yamada Y. A C-terminal fragment of fibulin-7 interacts with endothelial cells and inhibits their tube formation in culture. Arch Biochem Biophys, 545, 148-53, 2014.

    Ning L, Kurihara H, de Vega S, Ichikawa-Tomikawa N, Xu Z,Nonaka R, Kazuno S, Yamada Y, Miner JH, Arikawa-Hirasawa E. Laminin α1 regulates age-related mesangial cell proliferation and mesangial matrix accumulation through the TGFβ pathway. The American Journal of Pathology, 184, 1683-1694, 2014.

    Kerever A, Mercier F, Nonaka R, de Vega S, Oda Y, Zalc B, Okada Y, Hattori N, Yamada Y, Arikawa-Hirasawa E. Perlecan is required for FGF-2 signaling in the neural stem cell niche. Stem Cell Res., 12, 492-505, 2014.

    2013年

    Douet V, Arikawa-Hirasawa E, Mercier F. Fractone-heparan sulfates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone. Cell Prolif., 46, 137-145, 2013.

    Nakazawa N, Miyahara K, Okawada M, Yamataka A, Suzuki R, Akazawa C, Tomikawa-Ichikawa N, Arikawa-Hirasawa E. Laminin-1 promotes enteric nervous system development in mouse embryo. Pediatr Surg Int., 29, 1205-1208, 2013.

    Suzuki N, Numakawa T. Joshua Chou J, de Vega, S, Mizuniwa C, Sekimoto K, Adachi N, Kunugi N, Arikawa-Hirasawa E, Yamada Y, Akazawa C. Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling . The FASEB Journal, 28, 1386-1397, 2014.

    2012年

    Ichikawa-Tomikawa N, Ogawa J, Douet V, Xu Z, Kamikubo Y, Sakurai T, Kohsaka S, Chiba H, Hattori H, Yamada Y, Arikawa-Hirasawa E. Laminin a1 is essential for mouse cerebellar development. Matrix Biol., 31, 17–28, 2012.

    Mercier F, Arikawa-Hirasawa E. Heparan sulfate niche for cell proliferation in the adult brain. Neuroscience Letters, 5, 67-72, 2012.

    Yoshinaga H, Sakoda S, Good JM, Takahashi MP, Kubota T, Arikawa-Hirasawa E, Nakata T, Ohno K, Kitamura T, Kobayashi K, Ohtsuka Y. A novel mutation in SCN4A causes severe myotonia and school-age-onset paralytic episodes. Journal of the Neurological Sciences, 315, 15-19, 2012.

    Inomata T, Ebihara N, Funaki T, Matsuda A, Watanabe Y, Ning L, Xu Z, Murakami A, Arikawa-Hirasawa E. Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure. Ophthalmol Vis Sci.、 53, 1277-1284, 2012.

    Ishijima M, Suzuki N, Hozumi K, Matsunobu T, Kosaki K, Kaneko H, Hassell JR, Arikawa-Hirasawa E, Yamada Y. Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. Matrix Biol., 31. 234-245, 2012.

    Suzuki N, Fukushi M, Kosaki K, Doyle AD, de Vega S, Yoshizaki K, Akazawa C, Arikawa-Hirasawa E, Yamada Y. Teneurin-4 is a novel regulator of oligodendrocyte differentiation and myelination of small-diameter axons in the CNS. J Neurosci., 32. 11586-11599, 2012.

    Futami I, Ishijima M, Kaneko H, Tsuji K, Ichikawa-Tomikawa N, Sadatsuki R, Muneta T, Arikawa-Hirasawa E, Sekiya I, Kaneko K. Isolation and Characterization of Multipotential Mesenchymal Cells from the Mouse Synovium. PLoS One, 7, e45517, 2012.

    Douet V, Arikawa-Hirasawa E, Mercier F. Fractone-heparan sulfates mediate BMP-7 inhibition of cell proliferation in the adult subventricular zone. Neurosci Lett., 528, 120-125, 2012.

    2011年

    Ning L, Ishijima M, Kaneko H, Kurihara H, Arikawa-Hirasawa E, Kubota M, Liu L, Xu Z, Futami I, Yusup A, Miyahara K, Xu S, Kaneko K, Kurosawa H. Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis. Int. Orthop, 35, 831-838, 2011.

    Chyba M, Mercier F, Rader J, Douet V, Arikawa-Hirasawa E, Kwon YC, Kodama R. Dynamic mathematical modeling of cell-fractone interactions. Journal of Math-for-Industry, 3, 79–88, 2011.

    2010年

    Syu A, Ishiguro H, Inada T, Horiuchi Y, Tanaka S, Ishikawa M, Arai M, Itokawa M, Niizato K, Iritani S, Ozaki N, Takahashi M, Kakita A, Takahashi H, Nawa H, Keino-Masu K, Arikawa-Hirasawa E. Arinami T. Association of the HSPG2 gene with neuroleptic-induced tardive dyskinesia. Neuropsycho-pharmacology, 35, 1155-1164, 2010.

    Sakamoto Y, Ishijima M, Kaneko H, Kurebayashi N, Ichikawa N, Futami I, Kurosawa H, Arikawa-Hirasawa E. Distinct Mechanosensitive Ca2+ Influx Mechanisms in Human Primary Synovial Fibroblasts. J Orthop Res., 28, 859-864, 2010.

    Namba T, Yabe T, Gonda Y, Ichikawa N, Sanagi T, Arikawa-Hirasawa E, Mochizuki H, Kohsaka S, Uchino S. Pigment epithelium-derived factor up-regulation induced by memantine, an N-methyl-d-aspartate receptor antagonist, is involved in increased proliferation of hippocampal progenitor cells. Neuroscience, 167, 372-383, 2010.

    Xu Z, Ichikawa N, Kosaki K, Yamada Y, Sasaki T, Sakai LY Kurosawa H, Hattori N, Arikawa-Hirasawa E. Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition. Matrix Biol., 29, 461-470, 2010.

    Sasaki T, Takagi J, Giudici C, Yamada Y, Arikawa-Hirasawa E, Deutzmann R, Timpl R, Sonnenberg A, Bächinger HP, Tonge D. Laminin-121-Recombinant expression and interactions with integrins. Matrix Biol., 29, 484-493, 2010.

    2009年以前

    Ichikawa N, Iwabuchi K, Kurihara H, Ishii K, Kobayashi, Sasaki T, Hattori N,Mizuno Y, Hozumi K, Yamada Y, Arikawa-Hirasawa E. Binding of laminin-1 to GM1 ganglioside in lipid rafts is critical forneurite outgrowth. J Cell Sci., 122, 289-299, 2009.

    Arimura T, Hayashi YK, Murakami T, Oya Y, Funabe S, Arikawa-Hirasawa E, Hattori N, Nishino I, Kimura A. Mutational analysis of Fukutin gene in dilated cardiomyopathy and hypertrophic cardiomyopathy. Circulation Journal, 73, 158-161, 2009.

    Awamura Y, Uchida K, Arikawa-Hirasawa E. Long-term follow-up of laminin alpha2 (merosin)-deficient muscular dystrophy in a cat. J Feline Med Surg., 10, 274-279, 2008.

    Kerever A, Schnack J, Vellinga D, Ichikawa N, Moon C, Arikawa-Hirasawa E, Efird JT Mercier F. Novel Extracellular Matrix Structures in the Neural Stem Cell Niche Capture the Neurogenic Factor FGF-2 from the Extracellular Milieu. Stem Cells, 25, 2146-2157, 2007.

    Sher I, Zisman-Rozen S, Eliahu L, Whitelock JM, Maas-Szabowski N, Yamada Y, Breitkreutz D, Fusenig NE, Arikawa-Hirasawa E, Iozzo RV, Bergman R, Ron D. Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermal formation. J. Biol. Chem., 281, 5178-5187, 2006.

    Sugie K, Noguchi S, Kozuka Y, Arikawa-Hirasawa E, Tanaka M, Yan C, Saftig P, von Figura K, Hirano M, Ueno S, Nonaka I, Nishino I. Autophagic Vacuoles with Sarcolemmal Features Delineate Danon Disease and Related Myopathies. J Neuropathol Exp Neurol., 64, 513–522, 2005.

    Ichikawa N, Kasai S, Suzuki N, Nishi N, Oishi S, Fujii N, Kadoya Y, Hatori K, Mizuno Y, Nomizu M, Arikawa-Hirasawa E. Identification of neurite outgrowth active sites on the laminin alpha4 chain G domain. Biochemistry, 44, 5755-5762, 2005.

    Vikramadithyan RK, Kako Y, Chen G, Hu Y, Arikawa-Hirasawa E, Yamada Y, Goldberg IJ. Atherosclerosis in perlecan heterozygous mice. J Lipid Res., 45, 1806-1812, 2004.

    Yuasa K, Fukumoto S, Kamasaki Y, Yamada A, Fukumoto E, Kanaoka K, Saito K, Harada H, Arikawa-Hirasawa E, Miyagoe-Suzuki Y, Takeda S, Okamoto K, Kato Y, Fujiwara T. Laminin alpha2 essential for odontoblast differentiation regulating dentin sialoprotein expression. J Biol Chem., 279, 10286-10292, 2004.

    Arikawa-Hirasawa E, Le AH , Nishino I, Nonaka I, Ho NC, Francomano CA, Govindraj P, Hassell JR, Devaney JM, Spranger J, Stevenson RH, Iannaccone S, Dalakas MC, Yamada Y. Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia. Am. J. Hu. Gen.,70, 1368-1375, 2001.

    Arikawa-Hirasawa E, Yamada Y. Perlecan mutations in mice and humans: critical role of perlecan in skeletal development and disease. Acta Myologica, 20, 134-137, 2001.

    Arikawa-Hirasawa E, Wilcox RL, Govindraj P, Hassell JR, Yamada Y. Dyssegmental dysplasia, Silverman-Handmaker type, is caused by a functional null mutation of perlecan. Nature Genetics, 27, 431-434, 2001.

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