Functional characterization of LRRC8, a novel gene isolated from a patients with agammaglobulinemia, and its homologues.

• Project/Area Number: 15591105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: HARA Junichi (2004) Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助教授 (00238156); 松田 佳子 (2003) 大阪大学, 医学系研究科, 助手 (60343258)
• Co-Investigator(Kenkyū-buntansha): OHTA Hideaki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60322187) ; 時政 定雄 大阪大学, 医学部附属病院, 医員 ; 藤崎 弘之 大阪大学, 医学系研究科, 助手 ; 原 純一 大阪大学, 医学系研究科, 助手 (00238156)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: LRRC8 / LRRC8 family / B cell development

Research Abstract

We recently isolated a novel gene, leucine-rich repeat-containing 8 (LRRC8), from a translocation breakpoint in a patient with congenital agammaglobulinemia. In this study, we examined its function and searched its homologues, in order to further elucidate the role of LRRC8 in B cell development.
1)LRRC8 was expressed in peripheral B-cells and in mature BM B-cells. As for brain and spleen tissues, microphage lineage cells are positive for LRRC8.
2)There are four homologues of LRRC8, which show high similarity of sequences and belong to the LRRC8 family. Expression analysis using stimulators suggests that the members of this family might be implicated in proliferation and activation of lymphocytes and monocytes.
3)We did not detect any abnormalities of the LRRC8 gene structure and the protein expression in leukemia/lymphoma samples.
4)To further analyze the function of the gene, we are making LRRC8 deficient mice. We already made a targeting vector which deletes the exon 1 encompassing more than 80% of the gene, and are now inducing the vector into ES cells and making chimera mice.

Research Products

• [Journal Article] LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins (2004)
  • Author(s): Keiko K, Matsuda-Hashii Y, Hara J, et al.
  • Journal Title: FEBS Letters 564(1-2) Pages: 147-152
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins (2004)
  • Author(s): Kubota K, Kim JY, Sawada A, Tokimasa S, Fujisaki H, Matsuda-Hashii Y, Ozano K, Hara J.
  • Journal Title: FEBS Letters 564(1-2) Pages: 147-152
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A congenital mutation of the novel gene LRRC8 causes agammaglobuloinemia in humans (2003)
  • Author(s): Sawada A, Matsuda-Hashii Y, Hara J, et al.
  • Journal Title: J Clin Incest 112(11) Pages: 1707-1713
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans (2003)
  • Author(s): Sawada A, Takihara Y, Kim JY, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, Kubota K, Endo H, Onodera T, Ohta H, Ozono K, Hara J.
  • Journal Title: J Clin Incest. 112(11) Pages: 1707-1713
  • Description: 「研究成果報告書概要(欧文)」より