Creation of atopic dermatitis model mouse using double knock out mouse

• Project/Area Number: 22591240
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kagawa University
• Principal Investigator: YONEDA Kozo 香川大学, 医学部附属病院, 准教授 (60260626)
• Co-Investigator(Kenkyū-buntansha): KUBOTA Yasuo 香川大学, 医学部, 教授 (10126047) ; ARAKI Nobukazu 香川大学, 医学部, 教授 (10202748) ; NAKAI Kozo 香川大学, 医学部, 助教 (40363204)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2012: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2011: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2010: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: ロリクリン / ノックアウトマウス / 魚鱗癬 / アトピー性皮膚炎 / バリア / フレーキーテールマウス / フィラグリン

Research Abstract

Atopic dermatitis is one of intractable skin diseases. The clinical feature of this disease is itchy eczema. This disease is caused by mutations in filaggrin gene now. Loricrin is major constituent of marginal band of epidermal corneocyte. The clinical aspects of the variant form of Vohwinkel syndrome are mutilating keratoderma with ichthyosis. This phenotype is similar to ichthyosis vulgaris. Ichthyosis vulgaris is caused by homozygous or compound heterozygous mutations in the filaggrin gene. The aim of this project is creation of atopic dermatitis mouse model using loricrin knock out mouse.

Research Products

• [Journal Article] Detection of apoptotic keratinocytes in a case of bullous pemphigoid developed after graft-versus-host disease (2014)
  • Author(s): Yoneda K, Demitsu T, Kakurai M, Narita T, Nakai K, Kubota Y, Ishii N and Hashimoto T
  • Journal Title: Acta Derm Venereol Volume: 94 Pages: 231-232
• [Journal Article] Multi-branched acquired periungual fibrokeratoma (2014)
  • Author(s): Moriue T, Yoneda K, Moriue J, Nakai K and Kubota Y
  • Journal Title: JAMA Dermatol Volume: (Epub ahead of print) Issue: 4 Pages: 456-456
  • DOI: 10.1001/jamadermatol.2013.6631
• [Journal Article] Two cases of nevus sebaceous accompanying secondary tumors with Klothov expression (2014)
  • Author(s): Nakai K, Yoneda K, Haba R, Kushida Y, Katsuki N, Moriue J, Moriue T, Ishikawa E, Inoue S and Kubota Y
  • Journal Title: J Dermatol Volume: 41 Issue: 2 Pages: 171-172
  • DOI: 10.1111/1346-8138.12371
• [Journal Article] Novel ATP2A2 mutation in a patient with Darier disease (2014)
  • Author(s): Yoneda K, Demitsu T and Kubota Y
  • Journal Title: J Dermatol Volume: 41 Pages: 349-350
  • Peer Reviewed
• [Journal Article] A survey of the factors associated with concerns about oral antihistamine use in Japanese pruritic 30. Hosokawa Y, Yoneda K, Nakai K, Moriue J and Kubota Y: Completely thrombosed venous aneurysm in great saphenous vein (2013)
  • Author(s): Moriue J, Yoneda K, Nakai K, Hosokawa Y, Moriue T, and Kubota Y
  • Journal Title: Ann Dermatol Volume: 25 Pages: 268-270
• [Journal Article] Paraneoplastic pemphigus mimicking toxic epidermal necrolysis associated with B-cell lymphoma (2013)
  • Author(s): Yamada T, Nakamura S, Demitsu T, Nakamura T, Iida E, Yoneda K, Fukuda S and Hashimoto T
  • Journal Title: J Dermatol Volume: 40 Pages: 286-288
• [Journal Article] Dexamethasone induces caveolin-1 in vascular endothelial cells: implications for attenuated responses to VEGF (2013)
  • Author(s): Igarashi J, Hashimoto T, Shoji K, Yoneda K, Tsukamoto I, Moriue T, Kubota Y and Kosaka H
  • Journal Title: Am J Physiol Cell Physiol Volume: 304
• [Journal Article] Sphingosine 1-phosphate attenuates peroxide-induced apoptosis in HaCaT cells cultured in vitro (2013)
  • Author(s): Moriue T, Igarashi J, Yoneda K, Hashimoto T, Nakai K, Kosaka H and Kubota Y
  • Journal Title: Clin Exp Dermatol Volume: 38 Pages: 638-645
• [Journal Article] Primary dermal melanoma latent for more than 10 years (2013)
  • Author(s): Moriue J, Yoneda K, Moriue T, Nakai K, Katsuki N, Haba R, Ikeda M and Kubota Y
  • Journal Title: Ann Dermatol Volume: 25 Pages: 385-386
• [Journal Article] Successful treatment of primary cutenous anaplastic large cell lymphoma with intralesional methotrexate therapy (2013)
  • Author(s): Yokoi I, Ishikawa E, Koura A, Hosokawa Y, Tamai A, Nakai K, Moriue J, Moriue T, Yoneda K and Kubota Y
  • Journal Title: Acta Derm Venereol Volume: (Epub ahead of print) Issue: 3 Pages: 319-320
  • DOI: 10.2340/00015555-1692
• [Journal Article] Deranged epidermal differentiation in kl/kl mouse and the effects of Klotho siRNA on the differentiation of HaCaT cells (2013)
  • Author(s): Nakai K, Yoneda K, Haba R, Kushida Y, Katsuki N, Moriue T, Kosaka H, Kubota Y and Inoue S
  • Journal Title: Exp Dermatol Volume: (Epub ahead of print) Issue: 11 Pages: 772-774
  • DOI: 10.1111/exd.12258
• [Journal Article] Combination effects of cosmetic moisturisers in the topical treatment of acne vulgaris (2012)
  • Author(s): Munehiro A, Murakami Y, Shirahige Y, Nakai K, Moriue T, Matsunaka H, Yoneda K and Kubota Y
  • Journal Title: J Dermatol Treat Volume: 23 Pages: 172-176
• [Journal Article] A case of Degos disease successfully treated with corticosteroid combined with cyclophosphamide (2012)
  • Author(s): Kameda T, Dobashi H, Yoneda K, Susaki K, Kuno T, Murao K and Ishida T
  • Journal Title: Rheumatol Int Volume: 32 Pages: 2169-2173
• [Journal Article] Scedosporium apiospermum skin infection mimicking tuberous xanthoma (2012)
  • Author(s): Yoneda K, Nakai K, Moriue T, Ishikawa E, Demitsu T, Ohkusu K and Kubota Y
  • Journal Title: J Dermatol Volume: 39 Pages: 316-318
  • NAID: 10031184898
• [Journal Article] Numerous mucin nodules in a patient with seropositive wide spread discoid lupus erythematosus (2012)
  • Author(s): Yoneda K, Moriue J, Nakai K, Demitsu T, Moriue T, Yokoi I, Munehiro A, Dobashi H and Kubota Y
  • Journal Title: Ann Dermatol Volume: 24 Pages: 112-114
• [Journal Article] The profilaggrin N-terminal domain is absent in pityriasis rotunda (2012)
  • Author(s): Yoneda K, Presland RB, Demitsu T, Shimizu T and Kubota Y
  • Journal Title: Br J Dermatol Volume: 166 Pages: 227-229
• [Journal Article] Juvenile xanthogranuloma with lichenoid appearance (2012)
  • Author(s): Yoneda K, Demitsu T and Kubota Y
  • Journal Title: J Dermatol Volume: 39 Pages: 462-465
  • NAID: 10031184935
• [Journal Article] Interaction of the profilaggrin N-terminal domain with loricrin in human cultured keratinocytes and epidermis (2012)
  • Author(s): Yoneda K, Nakagawa T, Lawrence OT, Huard J, Demitsu T, Kubota Y and Presland RB
  • Journal Title: J Invest Dermatol Volume: 132 Pages: 1206-1214
• [Journal Article] Effect of sequential application of topical adapalene and clindamycin phosphate in the treatment of Japanese patients with acne vulgaris (2012)
  • Author(s): Kubota Y, Munehiro A, Shirahige Y, Nakai K, Katsuura J, Moriue T, Murakami Y, Matsunaka H and Yoneda K
  • Journal Title: J Dermatol Treat Volume: 23 Pages: 37-45
• [Journal Article] Inflammatory disseminated superficial porokeratosis with an unusual clinical feature of the pruritic, erythematous papules preceding annular brownish pigmentation (2012)
  • Author(s): Wakatabi K, Kakurai M, Yamada T, Umemoto N, Demitsu T and Yoneda K
  • Journal Title: J Dermatol Volume: 39 Pages: 946-948
• [Journal Article] Cutaneous Mycobacterium marinum infection mimicking felon in a patient with psoriatic arthritis treated with infliximab (2012)
  • Author(s): Demitsu T, Yamada T, Umemoto N, Narita T, Kakurai M and Yoneda K
  • Journal Title: J Dermatol Volume: 39 Pages: 970-971
• [Journal Article] Primary cutaneous cryptococcosis in a patient with CREST syndrome (2012)
  • Author(s): Ishikawa E, Yoneda K, Nakai K, Moriue J, Yokoi I, Munehiro A and Kubota Y
  • Journal Title: Eur J Dermatol Volume: 22 Pages: 421-422
• [Journal Article] Macular lymphocytic arteritis in a patient with rheumatoid arthritis (2012)
  • Author(s): Munehiro A, Yoneda K, Koura A, Nakai K and Kubota Y
  • Journal Title: Eur J Dermatol Volume: 22 Pages: 427-42
• [Journal Article] Pinch and ligation method: a new non-surgical approach to viral warts (2012)
  • Author(s): Moriue T, Yoneda K, Moriue J, Nakai K, Yokoi I, Fujita N, Munehiro A, Maeda R and Kubota Y
  • Journal Title: J Dermatol Volume: 39 Pages: 1108-1109
• [Journal Article] Pustular psoriasis precipitated by cytomegalovirus infection (2012)
  • Author(s): Yoneda K, Matsuoka-Shirahige Y, Demitsu T and Kubota Y
  • Journal Title: Br J Dermatol Volume: 167 Pages: 1186-1189
• [Journal Article] Reduced expression of epidermal growth factor receptor, E-cadherin, and occludin in the skin of flaky tail mice is due to filaggrin and loricrin deficiencies (2012)
  • Author(s): Nakai K, Yoneda K, Hosokawa Y, Moriue T, Presland RB, Fallon PG, Kabashima K, Kosaka H and Kubota Y
  • Journal Title: Am J Pathol Volume: 181 Pages: 969-977
• [Journal Article] Interaction of the Profilaggrin N-Terminal Domain with Loricrin in Human Cultured Keratinocytes and Epidermis (2012)
  • Author(s): Yoneda K, et al
  • Journal Title: Journal of Investigative Dermatology Volume: (印刷中)(Epub ahead of print) Issue: 4 Pages: 1206-14
  • DOI: 10.1038/jid.2011.460
  • Peer Reviewed
• [Journal Article] Reduced expression of epidermal growth factor receptor, E-cadherin, and occludin in the skin of flaky tail mice is due to filaggrin and loricrin deficiencies. (2012)
  • Author(s): Nakai K
  • Journal Title: Am J Pathol Volume: 181 Issue: 3 Pages: 969-77
  • DOI: 10.1016/j.ajpath.2012.06.005
  • Peer Reviewed
• [Journal Article] A founder effect of c.1938delC in ITGB4 underlies junctional epidermolysis bullosa and its application for prenatal testing (2011)
  • Author(s): Natsuga K, Nishie W, Shinkuma S, Nakamura H, Arita K, Yoneda K, Kusaka T, Yanagihara T, Kosaki R, Sago H, Akiyama M and Shimizu H
  • Journal Title: Exp Dermatol Volume: 20 Pages: 74-76
• [Journal Article] Lipid peroxidation-induced VEGF expression in the skin of KKAy obese mice (2011)
  • Author(s): Nakai K, Yoneda K, Ishihara Y, Ohmori K, Moriue T, Igarashi J, Kohno M, Kosaka H and Kubota Y
  • Journal Title: Exp Dermatol Volume: 20 Pages: 388-393
• [Journal Article] Skin infiltration of pelvic actinomycosis after total gastrectomy (2011)
  • Author(s): Yoneda K, Nakai K, Hosokawa Y, Moriue T, Demitsu T and Kubota Y
  • Journal Title: Eur J Dermatol Volume: 21 Pages: 290-291
• [Journal Article] Unilateral palm pompholyx in a patient with amyotrophic lateral sclerosis (2011)
  • Author(s): Nakai K, Yoneda K, Moriue T, Hosokawa Y, Yokoi I and Kubota Y
  • Journal Title: Eur J Dermatol Volume: 21 Pages: 445-446
• [Journal Article] Sarcoidosis presenting transepidermal elimination (2011)
  • Author(s): Yoneda K, Kakurai M, Umemoto N, Nakai K, Kubota Y and Demitsu T
  • Journal Title: Eur J Dermatol Volume: 21 Pages: 616-617
• [Journal Article] Consequences of two different amino-acid substitutions at the same codon in KRT14 indicate definitive roles of structural distortion in epidermolysis bullosa simplex pathogenesis (2011)
  • Author(s): Natsuga K, Nishie W, Smith BJ, Shinkuma S, Smith TA, Parry DA, Oiso N, Kawada A, Yoneda K, Akiyama M and Shimizu H
  • Journal Title: J Invest Dermatol Volume: 131 Pages: 1869-1876
• [Journal Article] Activation of vascular endothelial growth factor receptor 2 in a cellular model of loricrin keratoderma (2010)
  • Author(s): Yoneda K, Demitsu T, Nakai K, Moriue T, Ogawa W, Igarashi J, Kosaka H and Kubota Y
  • Journal Title: J Biol Chem Volume: 285 Pages: 16184-16194
• [Journal Article] Community-based epidemiological study of psychosocial effects of acne in Japanese adolescents (2010)
  • Author(s): Kubota Y, Shirahige Y, Nakai K, Katsuura J, Moriue T and Yoneda K
  • Journal Title: J Dermatol Volume: 37 Pages: 617-622
  • NAID: 10026637291
• [Journal Article] Clinical efficacy of reserpine as "add-on therapy" to antihistamines in patients with recalcitrant chronic idiopathic urticaria and urticarial vasculitis (2010)
  • Author(s): Demitsu T, Yoneda K, Kakurai M, Sasaki K, Hiratsuka Y, Azuma R, Yamada T and Umemoto N
  • Journal Title: J Dermatol Volume: 37 Pages: 827-829
  • NAID: 10027067334
• [Journal Article] Bevacizumab-induced hand-foot syndrome: circumscribed type (2010)
  • Author(s): Munehiro A, Yoneda K, Nakai K, Demitsu T, Moriue T, Moriue J, Yokoi I, Fujita N, Matsuura N, Ishikawa S, Yokomise H and Kubota Y
  • Journal Title: Br J Dermatol Volume: 162 Pages: 1411-1413
• [Journal Article] Expression of wild-type, but not mutant, loricrin causes programmed cell death in HaCaT keratinocytes (2010)
  • Author(s): Yoneda K, Demitsu T, Manabe M, Igarashi J, Kosaka H, Inagaki N, Takahashi H, Kon A, Kakurai M and Kubota Y
  • Journal Title: J Dermatol Volume: 37 Pages: 956-964
  • NAID: 10027572660
• [Journal Article] Late radiation dermatitis of the right arm after cardiac catheterization (2010)
  • Author(s): Yoneda K, Nakai K, Demitsu T, Moriue T, Moriue J, Yokoi I, Munehiro A, Noma T, Kohno M and Kubota Y
  • Journal Title: Eur J Dermatol Volume: 20 Pages: 654-656
• [Journal Article] Seborrhoeic keratoses and acanthosis nigricans in a long-term survivor of thanatophoric dysplasia (2010)
  • Author(s): Nakai K, Yoneda K, Moriue T, Munehiro A, Fujita N, Moriue J, Yokoi I, Haba R, Itoh S and Kubota Y
  • Journal Title: Br J Dermatol Volume: 163 Pages: 656-658
• [Journal Article] Activation of Vascular Endothelial Growth Factor Receptor 2 in a Cellular Model of Loricrin Keratoderma (2010)
  • Author(s): Yoneda K, et al.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 16184-16194
  • Peer Reviewed
• [Journal Article] Zosteriform cutaneous metastasis of lung adenocarcinoma
  • Author(s): Kubota Y, Nakai K, Munehiro A, Moriue J and Yoneda K
  • Journal Title: J Clin Exp Dermatol Res Volume: 36 (in press)
• [Journal Article] Pachyonychia congenita in Japan: report of familial cases with a recurrent KRT16 mutation and review of the literature
  • Author(s): Inaba Y, Kanazawa N, Furukawa F, Sakurane Y, Nakano H, Sawamura D, Yoneda K, Hamada T and Hashimoto T
  • Journal Title: Eur J Dermatol Volume: (in press)
• [Presentation] Cytomegalovirus infection is one of the precipitating factors for pustular psoriasis (2012)
  • Author(s): Yoneda K, Matsuoka-Shirahige Y, Demitsu T and Kubota Y
  • Organizer: The 37^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Year and Date: 2012-12-07
• [Presentation] Klotho regulates the differentiation and tumorgenesis of epidermal keratinocytes (2012)
  • Author(s): Nakai K, Inoue S, Haba R, Kushida Y, Katsuki N, Hosokawa Y, Moriue T, Yoneda K and Kubota Y
  • Organizer: The 37^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Year and Date: 2012-12-07
• [Presentation] Reduced expression of EGF receptor, E-cadherin and occludin is due to loricrin deficiency in the skin of flaky tail mice (2011)
  • Author(s): Nakai K, Yoneda K, Hosokawa Y, Moriue T and Kubota Y
  • Organizer: The 36^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Kyoto
  • Year and Date: 2011-12-09
• [Presentation] Direct effects of bevacizumab on cell proliferation and cell signaling pathways in HaCaT cells (2011)
  • Author(s): Hosokawa Y, Yoneda K, Moriue T, Nakai K and Kubota Y
  • Organizer: The 36^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Kyoto
  • Year and Date: 2011-12-09
• [Presentation] The profilaggrin N-terminal domain is absent in pityriasis rotunda (2011)
  • Author(s): Yoneda K, Presland RB, Demitsu T, Shimizu T and Kubota Y
  • Organizer: The 36^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Kyoto
  • Year and Date: 2011-12-09
• [Presentation] Abnormally aggregated caveolin-1 in the cytoplasm of cellular model of classic Vohwinkel syndrome (2010)
  • Author(s): Yoneda K, Nakai K, Moriue T, Demitsu T and Kubota Y
  • Organizer: The 35^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Wakayama
  • Year and Date: 2010-12-04
• [Presentation] The effects of oxidized LDL on VEGF production in HaCaT cells: a possible mechanism for psoriasis in metablic syndrome (2010)
  • Author(s): Nakai K, Yoneda K, Ishihara Y, Ohmori K, Moriue T, Igarashi J, Kohno M, Kosaka H and Kubota Y
  • Organizer: The 35^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Wakayama
  • Year and Date: 2010-12-03
• [Presentation] Pitavastatin suppresses lipid peroxidation-induced VEGF expression in the skin of KKAy metabolic syndrome mice (2010)
  • Author(s): Nakai K, Yoneda K, Ishihara Y, Ohmori K, Moriue T, Igarashi J, Kohno M, Kosaka H and Kubota Y
  • Organizer: 17^<th> Annual Meeting of The Society for Free Radical Biology and Medicine
  • Place of Presentation: Orlando
  • Year and Date: 2010-11-18
• [Presentation] ロリクリン角皮症モデル細胞におけるシグナル伝達について
  • Author(s): 米田耕造
  • Organizer: 第28回角化症研究会
  • Place of Presentation: 沖縄
  • Invited