Innovation of novel treatment and fetal therapy for ichthyosis

• Project/Area Number: 20390304
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nagoya University (2010); Hokkaido University (2008-2009)
• Principal Investigator: AKIYAMA Masashi 名古屋大学, 大学院・医学系研究科, 教授 (60222551)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Hiroshi 北海道大学, 大学院・医学研究科, 教授 (00146672) ; ABE Riichiro 北海道大学, 大学院・医学研究科, 准教授 (60344511)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 遺伝子 / 角化 / 魚鱗癬 / 胎児治療

Research Abstract

In the present project, in order to innovate a novel therapy for ichhthyosis, we made a normal human ABCA12 gene construct, and performed transfection experiments of the construct into the cultured keratinocytes from ichthyosis patients and ABCA12-disrupted mice(ichthyosis model mice). We reconstructed ichthyosis lesions from the transfected keratinocytes and evaluated treatment efficacy of transfected ABCA12 gene constructs. In addition, we performed treatment experiments to fetuses of ABCA12-disrupted mice. From the results, we obtained clues to establish novel effective treatment against congenital ichthyosis.

Research Products

• [Journal Article] CYP4F22 is highly expressed at the site and onset of keratinization during human skin development (2012)
  • Author(s): Sasaki K, Akiyama M, Yanagi T, Sakai K, Miyamura Y, Sato M, Shimizu H
  • Journal Title: J Dermatol Sci Volume: 65 Pages: 156-158
  • Peer Reviewed
• [Journal Article] Extremely severe palmoplantar hyperkeratosis in a generalized epidermolytic hyperkeratosis patient with a keratin 1 gene mutation (2011)
  • Author(s): Osawa R, Akiyama M, Izumi K, Ujiie H, Sakai K, Nemoto-Hasebe I, Yanagi T, Koizumi H, Shimizu H
  • Journal Title: J Am Acad Dermatol Volume: 64 Pages: 991-993
  • Peer Reviewed
• [Journal Article] New insight into genotype/phenotype correlations in ABCA12 mutations in harlequin ichthyosis (2011)
  • Author(s): Umemoto H, Akiyama M, Yanagi T, Sakai K, Aoyama Y, Oizumi A, Suga Y, Kitagawa Y, Shimizu H
  • Journal Title: J Dermatol Sci Volume: 61 Pages: 136-138
  • Peer Reviewed
• [Journal Article] AKT has an anti-apoptotic role in ABCA12-deficient keratinocytes (2011)
  • Author(s): Yanagi T, Akiyama M, Nishihara H, Miyamura Y, Sakai K, Tanaka S, Shimizu H
  • Journal Title: J Invest Dermatol Volume: 131 Pages: 1942-1945
  • Peer Reviewed
• [Journal Article] Abca12-mediated lipid transport and snap29-dependent trafficking of lamellar granules are critical for epidermal morphogenesis in Zebrafish Disease Model of Ichthyosis (2011)
  • Author(s): Li Q, Frank M, Akiyama M, Shimizu H, Ho S-Y, Thisse C, Thisse B, Sprecher E, Uitto J
  • Journal Title: Dis Model Mech Volume: 4 Pages: 777-785
  • Peer Reviewed
• [Journal Article] The roles of ABCA12 in keratinocyte differentiation and lipid barrier formation in the epidermis (2011)
  • Author(s): Akiyama M
  • Journal Title: Dermato-Endocrinology Volume: 3 Pages: 107-112
  • Peer Reviewed
• [Journal Article] Updated molecular genetics and pathogenesis of ichthyoses (2011)
  • Author(s): Akiyama M
  • Journal Title: Nagoya J Med Sci Volume: 73 Pages: 79-90
  • NAID: 120003277468
  • Peer Reviewed
• [Journal Article] Malignant skin tumours in patients with inherited ichthyosis (2011)
  • Author(s): Natsuga K, Akiyama M, Shimizu H
  • Journal Title: Br J Dermatol Volume: 165 Pages: 263-268
  • Peer Reviewed
• [Journal Article] Transglutaminase1 preferred substrate peptide K5 is an efficient tool in diagnosis of lamellar ichthyosis (2010)
  • Author(s): Akiyama M, Sakai K, Yanagi T, Fukushima S, Ihn H, Hitomi K, Shimizu H
  • Journal Title: Am J Pathol Volume: 176 Pages: 1592-1599
  • Peer Reviewed
• [Journal Article] An Indian family with Sjogren-Larsson syndrome caused by a novel ALDH3A2 mutation (2010)
  • Author(s): Sakai K, Akiyama M, Yanagi T, Nampoothiri S, Mampilly T, V S, Shimizu H
  • Journal Title: Int J Dermatol Volume: 49 Pages: 1031-1033
  • Peer Reviewed
• [Journal Article] Revised nomenclature and classification of inherited ichthyoses : Results of the First Ichthyosis Consensus Conference in Soreze 2009 (2010)
  • Author(s): Oji V, Tadini G, Akiyama M, Blanchet-Bardon C, Bodemer C, Bourrat E, Coudiere P ; DiGiovanna JJ, Elias P, Fischer J, Fleckmann P, Gina M, Harper J, Hashimoto T, Hausser I, Hennies HC, Hohl D, Hovnanian A, Ishida-Yamamoto A, Jacyk WK, Leachman S, Leigh I, Mazereeuw-Hautier J, Milstone L, Morice-Picard F, Paller AS, Richard G, Schmuth M, Shimizu H, Sprecher E, vanSteensel M, Taieb A, Toro JR, Vabres P, Vahlquist A, Williams M, Traupe H
  • Journal Title: J Am Acad Dermatol Volume: 63 Pages: 607-641
  • Peer Reviewed
• [Journal Article] Partially disturbed lamellar granule secretion in mild congenital ichthyosiform erythroderma with ALOX12B mutations (2010)
  • Author(s): Akiyama M, Sakai K, Yanagi T, Tabata N, Yamada M, Shimizu H
  • Journal Title: Br J Dermatol Volume: 163 Pages: 201-204
  • Peer Reviewed
• [Journal Article] Self-improvement of keratinocyte differentiation defects during skin maturation in ABCA12 deficient harlequin ichthyosis model mice (2010)
  • Author(s): Yanagi T, Akiyama M, Nishihara H, Ishikawa J, Sakai K, Miyamura Y, Naoe A, Kitahara T, Tanaka S, Shimizu H
  • Journal Title: Am J Pathol Volume: 177 Pages: 106-118
  • Peer Reviewed
• [Journal Article] Neutral lipid storage leads to acylceramide deficiency, likely contributing to the pathogenesis ofDorfman-Chanarin syndrome (2010)
  • Author(s): Uchida Y, Cho Y, Moradian S, Kim J, Nakajima K, Crumrine D, Park K, Ujihara M, Akiyama M, Shimizu H, Holleran WM, Sano S, Elias PM
  • Journal Title: J Invest Dermatol Volume: 130 Pages: 2497-2499
  • Peer Reviewed
• [Journal Article] ABCA12 dysfunction causes a disorder in glucosylceramide accumulation during keratinocyte differentiation (2010)
  • Author(s): Mitsutake S, Suzuki C, Akiyama M, Tsuji K, Yanagi T, Shimizu H, Igarashi Y
  • Journal Title: J Dermatol Sci Volume: 60 Pages: 128-129
  • NAID: 10027474089
  • Peer Reviewed
• [Journal Article] ABCA12 mutations and autosomal recessive congenital ichthyosis : A review of genotype/phenotype correlations and of pathogenetic concepts (2010)
  • Author(s): Akiyama M
  • Journal Title: Hum Mutation Volume: 31 Pages: 1090-1096
  • Peer Reviewed
• [Journal Article] Transglutaminase 1 preferred substrate peptide K5 is an efficient tool in diagnosis of lamellar ichthyosis (2010)
  • Author(s): Akiyama M
  • Journal Title: Am J Pathol Volume: 176 Pages: 1592-1599
  • Peer Reviewed
• [Journal Article] Current advances in gene the rapy for thetreatment of genodermatoses (2009)
  • Author(s): Long HA, McMillan JR, Qiao H, Akiyama M, Shimizu H
  • Journal Title: Curr Gene Ther Volume: 9 Pages: 487-494
  • Peer Reviewed
• [Journal Article] Conradi-Hunermann-Happle syndrome with abnormal lamellar granule contents (2009)
  • Author(s): Akiyama M, Sakai K, Hayasaka K, TabataN, Yamada M, Ujiie H, Shibaki A, Shimizu H
  • Journal Title: Br J Dermatol Volume: 160 Pages: 1335-1337
  • Peer Reviewed
• [Journal Article] ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma (2009)
  • Author(s): Sakai K, Akiyama M, Yanagi T, McMillanJR, Suzuki T, Tsukamoto K, Sugiyama H, Hatano Y, Hayashitani M, Takamori K, Nakashima Keiko, Shimizu H
  • Journal Title: J Invest Dermatol Volume: 129
  • Peer Reviewed
• [Journal Article] Novel mutation p. Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss (2009)
  • Author(s): Nemoto-Hasebe I, Akiyama M, Kudo S, Ishiko A, Tanaka A, Arita K, Shimizu H
  • Journal Title: B J Dermatol Volume: 161 Pages: 452-455
  • Peer Reviewed
• [Journal Article] Ceramide stimulates ABCA12 expression via peroxisome proliferators-activated receptorδin human keratinocytes (2009)
  • Author(s): Jiang YJ, Uchida Y, Lu B, Kim P, Mao C, Akiyama M, Elias PM, Holleran WM, Grunfeld C, Feingold KR
  • Journal Title: J Biol Chem Volume: 284 Pages: 18942-18952
  • Peer Reviewed
• [Journal Article] Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss. (2009)
  • Author(s): Nemoto-Hasebe I
  • Journal Title: Br J Dermatol 161 Pages: 452-455
  • Peer Reviewed
• [Journal Article] Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan (2008)
  • Author(s): Nomura T, Akiyama M, Sandilands A, Nemoto-Hasebe I, Sakai K, Nagasaki A, Ota M, Hata H, Evans AT, Palmer CAN, Shimizu H, McLean WHI
  • Journal Title: J Invest Dermatol Volume: 128 Pages: 1436-1441
  • Peer Reviewed
• [Journal Article] Novel compound heterozygous nonsense and missense ABCA12 mutations lead to non-bullous congenital ichthyosiformerythroderma (2008)
  • Author(s): Akiyama M, Sakai K, Hatamochi A, Yamazaki S, McMillan JR, Shimizu H
  • Journal Title: Br J Dermatol Volume: 158 Pages: 864-867
  • Peer Reviewed
• [Journal Article] Mild recessive bullous congenital ichthyosiform erythroderma due to a novel homozygous keratin 10 nonsense mutation (2008)
  • Author(s): Tsubota A, Akiyama M, Kanitakis J, Sakai K, Nomura T, Claudy A, Shimizu H
  • Journal Title: J Invest Dermatol Volume: 128 Pages: 1648-1652
  • Peer Reviewed
• [Journal Article] DNA-based prenatal exclusion of harlequin ichthyosis (2008)
  • Author(s): Yanagi T, Akiyama M, Sakai K, Nagasaki A, Ozawa N, Kosaki R, Sago H, Shimizu H
  • Journal Title: J Am Acad Dermatol Volume: 58 Pages: 653-656
  • Peer Reviewed
• [Journal Article] Keratitis-Ichthyosis-Deafness syndrome lacking subjective hearing impairment (2008)
  • Author(s): Nemoto-Hasebe I, Akiyama M, Yanada N, Inoue Y, Chizu T, Shimizu H
  • Journal Title: Acta Dermato-Venereol Volume: 88 Pages: 406-408
  • Peer Reviewed
• [Journal Article] Harlequin ichthyosis model mouse reveals alveolar collapse and fetal skin barrier defects (2008)
  • Author(s): Yanagi T, Akiyama M, Nishihara H, Sakai K, Nishie W, Tanaka S, Shimizu H
  • Journal Title: Hum Mol Genet Volume: 17 Pages: 3075-3083
  • Peer Reviewed
• [Journal Article] CGI-58 is an alpha/beta hydrolase within lipid transporting lamellar granules of differentiated keratinocytes (2008)
  • Author(s): Akiyama M, Sakai K, Takayama C, Yanagi T, Yamanaka Y, McMillan JR, Shimizu H
  • Journal Title: Am J Pathol Volume: 173 Pages: 1349-60
  • Peer Reviewed
• [Journal Article] An update on molecular aspects of the non-syndromic ichthyoses (2008)
  • Author(s): Akiyama M, Shimizu H
  • Journal Title: Exp Dermatol Volume: 17 Pages: 373-382
  • Peer Reviewed
• [Journal Article] Harlequin ichthyosis model mouse reveals alveolar collapse and fetal skinbarrier defects (2008)
  • Author(s): Yanagi T
  • Journal Title: Hum Mol Genet 17 Pages: 3075-3083
  • Peer Reviewed
• [Journal Article] CGI-58 is an alpha / beta hydrolase within lipid transporting lamellargranules of differentiated keratinocytes (2008)
  • Author(s): Akiyama M
  • Journal Title: Am J Pathol 173 Pages: 1349-1360
  • Peer Reviewed
• [Journal Article] Transglutaminasel preferred substrate peptide K5 is an efficient tool in diagnosis of lamellar ichthyosis.
  • Author(s): Akiyama M
  • Journal Title: Am J Pathol (印刷中)
  • Peer Reviewed
• [Journal Article] Self-improvement of keratinocyte differentiation defects during skin maturation in ABCA12 deficient harlequin ichthyosis model mice.
  • Author(s): Yanagi T
  • Journal Title: Am J Pathol (印刷中)
  • Peer Reviewed
• [Journal Article] Prevalent LIPH Founder Mutations Lead to Loss of P2Y5 Activation Ability of PA-PLA_1α in Autosomal Recessive Hypotrichosis.
  • Author(s): Shinkuma S
  • Journal Title: Human Mutation (印刷中)
  • Peer Reviewed
• [Journal Article] ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma
  • Author(s): Sakai K
  • Journal Title: J Invest Dermatol (印刷中)
  • Peer Reviewed
• [Journal Article] Conradi-Hunermann-Happle syndrome with abnormal lamellar granule contents
  • Author(s): Akiyama M
  • Journal Title: Br J Dermatol (印刷中)
  • Peer Reviewed
• [Presentation] ABC Proteins and Disorders ; ABCA12 andharlequin ichthyosis (2011)
  • Author(s): Akiyama M
  • Organizer: ABC Proteins/Membrane Meso-Domains/ES-iPS Cells
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-11-17
• [Presentation] ABC Proteins and Disorders ; ABCA12 and harlequin ichthyosis (2011)
  • Author(s): Akiyama M
  • Organizer: ABC 2011 in Kyoto, ABC Proteins/Membrane Meso-Domains/ES-iPS Cells
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-11-17
• [Presentation] Synthetic Peptide K5 Efficiently Detects in situ Transglutaminase1 Activity ; Its Application for Diagnosis of Lamellar Ichthyosis (2010)
  • Author(s): Akiyama M
  • Organizer: The 40th European Society for Dermatological Research(ESDR) Annual Meeting
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2010-09-11
• [Presentation] Synthetic Peptide K5 Efficiently Detects in situ Transglutaminase 1 Activity ; Its Application for Diagnosis of Lamellar Ichthyosis (2010)
  • Author(s): Akiyama M
  • Organizer: The 40th European Society for Dermatological Research (ESDR) Annual Meeting
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2010-09-11
• [Presentation] Keratinocyte lipid transporter ABCA12 plays a key role in epidermal keratinization and barrier function (2010)
  • Author(s): Akiyama M
  • Organizer: The 27th Naito Conference on Membrane Dynamics and Lipid Biology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2010-07-01
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/derma/ABCA12/index.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/derma/ABCA12/index.html