Making of the management method for breast milk jaundice using transgenic mice

• Project/Area Number: 15K09710
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Shiga University of Medical Science
• Principal Investigator: MARUO YOSHIHIRO 滋賀医科大学, 医学部, 教授 (80314160)
• Co-Investigator(Kenkyū-buntansha): 藤原 亮一 北里大学, 薬学部, 講師 (40631643) ; 松井 克之 滋賀医科大学, 医学部, 講師 (60595924)
• Research Collaborator: Tukey Robert H ; Yanagi Takahide
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 母乳性黄疸 / 遺伝性非抱合型高ビリルビン血症 / ビリルビンUDP-グルクロン酸転移酵素 / UGT1A1 / Gilbert症候群 / 新生児 / 核黄疸 / 新生児高ビリルビン血症 / 新生児黄疸 / 体質性黄疸

Outline of Final Research Achievements

For the safety management of brest milk jaundice (BMJ), I performed analysis UGT1A1 gene in infants with BMJ. I revealed UGT1A1*6 (p.G71R) variant which is a genetic cause of BMJ is also important cause for Gilbert syndrome (Maruo Y. J Pediatr 2016). UGT1A1*28 which is other important variant was also the cause of Gilbert syndrome but not a cause of BMJ. UGT1A1*6 is also the genetic cause of BMJ in low birth weight infants (Yanagi T. J Pediatr 2017) and a risk factor kernicteric in extreme preterm indants (Yanagi T. submitted).
I made p.G71R-humanized UGT1A mice in collaboration with Prof. Tukey in University of California San Diego. The mice will be brought to our laboratory and I continue further study.

Academic Significance and Societal Importance of the Research Achievements

母乳性黄疸は後期新生児期にみられる母乳栄養に関連する遷延性高ビリルビン血症である。多くの赤ちゃんにみられ、核黄疸の危険性がある場合もある。そのため母乳性黄疸の背景を明らかにして、管理法を確立することは子育てをする家族や赤ちゃん自身の健康に寄与する。また、超早産児の核黄疸発生を予防するための研究にもつながり、社会に広く貢献するものと考える。

Research Products

• [Int'l Joint Research] University of California San Diego(米国)
• [Int'l Joint Research] University of California, San Diego(米国)
• [Int'l Joint Research] UC Sandiego(米国)
• [Int'l Joint Research] UC San Diego(米国)
• [Journal Article] Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (2019)
  • Author(s): Okano T, Imai K, Tsujita Y, Mitsuiki N, Yoshida K, Kamae C, Maruo Y, et al.
  • Journal Title: J Allergy Clin Immunol Volume: 143 Pages: 266-275
  • Peer Reviewed / Open Access
• [Journal Article] X-linked Charcot-Marie-Tooth disease type 5 with recurrent weakness after febrile illness (2019)
  • Author(s): Nishikura N, Yamagata T, Morimune T, Matsui J, Sokoda T, Sawai C, Sakaue Y, Higuchi Y, Hashiguchi A, Takashima H, Takeuchi Y, Maruo Y
  • Journal Title: Brain Dev Volume: 41 Pages: 201-204
  • Peer Reviewed / Open Access
• [Journal Article] Postnatal developmental changes in the sensitivity of L-type Ca2+ channel to inhibition by verapamil in a mouse heart model (2018)
  • Author(s): Sagawa Hironori、Hoshino Shinsuke、Yoshioka Kengo、Ding Wei-Guang、Omatsu-Kanbe Mariko、Nakagawa Masao、Maruo Yoshihiro、Matsuura Hiroshi
  • Journal Title: Pediatr Res Volume: in press Pages: 1207-1217
  • DOI: 10.1038/pr.2018.46
  • Peer Reviewed / Open Access
• [Journal Article] The histological findings in transposition of the great artery with severe persistent pulmonary hypertension of the newborn (2018)
  • Author(s): Hoshino S, Somura J, Furukawa O, Yanagi T, Maruo Y
  • Journal Title: J Cardiol Cases Volume: 2018 Pages: 159-162
  • Peer Reviewed / Open Access
• [Journal Article] Bilirubin Uridine Diphosphate-glucuronosyltransferase Polymorphism as a Risk Factor for Prolonged Hyperbilirubinemia in Japanese Preterm Infants (2017)
  • Author(s): Yanagi Takahide、Nakahara Sayuri、Maruo Yoshihiro
  • Journal Title: Journal of Pediatrics Volume: 190 Pages: 159-162
  • DOI: 10.1016/j.jpeds.2017.07.014
  • Peer Reviewed
• [Journal Article] Gilbert Syndrome with Concomitant Hereditary Spherocytosis Presenting with Moderate Unconjugated Hyperbilirubinemia (2017)
  • Author(s): Aiso M, Yagi M, Tanaka A, Miura K, Miura R, Arizumi T, Takamori Y, Nakahara S, Maruo Y, Takikawa H
  • Journal Title: Intern. Med. Volume: 56 Issue: 6 Pages: 661-664
  • DOI: 10.2169/internalmedicine.56.7362
  • NAID: 130005450367
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Does acid etching morphologically and chemically affect lithium disilicate glass ceramic surfaces? (2017)
  • Author(s): Maruo Y, Nishigawa G, Irie M, Yoshihara K, Matsumoto T, Minagi S.
  • Journal Title: JOURNAL OF APPLIED BIOMATERIALS AND FUNCTIONAL MATERIALS Volume: 15 Pages: 93-100
  • DOI: 10.5301/jabfm.5000303
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type II and Gilbert syndrome. (2016)
  • Author(s): Maruo Y, Nakahara S, Yanagi T, Nomura A, Mimura Y, Matsui K, Sato H, Takeuchi Y
  • Journal Title: J Gastroenterol Hepatol Volume: 31 Pages: 403-408
  • DOI: 10.1111/jgh.13071
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Natural course of congenital hypothyroidism by dual oxidase 2 mutations from the neonatal period through puberty. (2016)
  • Author(s): Maruo Y, Nagasaki K, Matsui K, Mimura Y, Mori A, Fukami M, Takeuchi Y
  • Journal Title: Eur J Endocrinol Volume: 174 Pages: 453-463
  • DOI: 10.1530/eje-15-0959
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report. (2016)
  • Author(s): Maruo Y, Mori A, Morioka Y, Sawai C, Mimura Y, Matui K, Takeuchi Y.
  • Journal Title: BMC Endocr Disord Volume: 16 Pages: 1-1
  • DOI: 10.1186/s12902-015-0081-7
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Contribution of UGT1A1 variations to chemotherapy-induced unconjugated hyperbilirubinemia in pediatric leukemia patients. (2016)
  • Author(s): Nomura A, Maruo Y, Taga T, Takeuchi Y.
  • Journal Title: Pediatr Res Volume: 202 Pages: 252-257
  • DOI: 10.1038/pr.2016.75
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase delta syndrome-like immunodeficiency. (2016)
  • Author(s): Tsujita Y, et al.
  • Journal Title: J Allergy Clin Immunol Volume: 138 Pages: 1672-1680
  • DOI: 10.1016/j.jaci.2016.03.055
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Steroid Pulse Therapy for Kawasaki Disease Complicated with Myocarditis. (2016)
  • Author(s): Sato T, Somura J, Maruo Y.
  • Journal Title: Indian Pediatr Volume: 53 Pages: 1015-1016
  • Peer Reviewed / Open Access
• [Journal Article] Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia. (2015)
  • Author(s): Fujiwara R, Maruo Y, Chen S, Tukey RH
  • Journal Title: Toxicology and Applied Pharmacology Volume: 289 Pages: 124-132
  • DOI: 10.1016/j.taap.2015.08.018
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Two Different UGT1A1 Mutations causing Crigler-Najjar Syndrome types I and II in an Iranian Family. (2015)
  • Author(s): Maruo Y, Behnam M, Ikushiro S, Nakahara S, Nouri N, Salehi M.
  • Journal Title: J Gastrointestin Liver Dis. Volume: 24 Pages: 523-526
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel large deletion (exons 12, 13) and a missense mutation (p.G46R) in the PAH in a Japanese patient with phenylketonuria. (2015)
  • Author(s): Maruo Y, Suzaki M, Matsui K, Mimura Y, Mori A, Shintaku H, Takeuchi Y.
  • Journal Title: World J Pediatr Volume: 11 Pages: 181-184
  • DOI: 10.1007/s12519-015-0020-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neonatal Meckel diverticulum: Obstruction due to a short mesodiverticular band. (2015)
  • Author(s): Kunitsu T, Koshida S, Tanaka K, Nakahara S, Yanagi T, Maruo Y,
  • Journal Title: Pediatr Int Volume: 57 Pages: 1007-1009
  • DOI: 10.1111/ped.12694
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Escherichia coli O121:H19 infection identified on microagglutination assay and PCR. (2015)
  • Author(s): Sakai T, Sawai T, Shimizu Y, Morimune T, Okuda Y, Maruo Y, Iyoda S, Takeuchi Y.
  • Journal Title: Pediatr Int Volume: 57 Pages: 1001-1003
  • DOI: 10.1111/ped.12699
  • Peer Reviewed / Int'l Joint Research
• [Presentation] ビリルビンUDP-グルクロン酸転移酵素と新生児黄疸 (2018)
  • Author(s): 丸尾良浩
  • Organizer: 第５回大阪小児科医会総会・教育セミナー
  • Invited
• [Presentation] ビリルビンUDP-グルクロン酸転移酵素と黄疸 (2017)
  • Author(s): 丸尾良浩
  • Organizer: 第44回日本小児栄養消化器肝臓学会
  • Invited
• [Presentation] Yoshihiro Maruo, Keisuke Nagasaki, Katsuyuki Matsui, Yu Mimmura, Asami Mori, Maki Fukami, Yoshihiro Takeuchi (2016)
  • Author(s): Natural course of congenital hypothyroidism by dual oxidase 2 mutations from the neonatal period through puberty.
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都市
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Neonatal Hemochromatosis detected by galactosemia at newborn screening. (2015)
  • Author(s): Takashima K, Maruo Y, Tsutsui H, Yanagi T, Kasahara M, Takeuchi Y.
  • Organizer: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Annual Meeting.
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] Bilirubin UDP-Glucuronosyltransferase Variation Is a Genetic Basis of Breast Milk Jaundice. (2015)
  • Author(s): Maruo Y, Yanagi T, Tukey RH
  • Organizer: Pediatric Academic Societies, annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-04-25
  • Int'l Joint Research
• [Presentation] Bilirubin Uridine Diphospahate-glucuronosyltransferase polymorpshism is a risk factor for prolonged unconjugated hyperbilirubinema in preterm infants. (2015)
  • Author(s): Yanagi T, Nakahara S, Maruo Y
  • Organizer: Pediatric Academic Societies, annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-04-25
  • Int'l Joint Research
• [Remarks] Detection and Models of Toxicant Exposure
  • URL: http://superfund.ucsd.edu