| Project/Area Number |
17390490
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Tsurumi University |
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Principal Investigator |
SAITO Ichiro Tsurumi University, School of Dental Medicine, Professor, 歯学部, 教授 (60147634)
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| Co-Investigator(Kenkyū-buntansha) |
MISHIMA Kenji Tsurumi University, School of Dental Medicine, Associate Professor, 歯学部, 助教授 (50275343)
INOUE Hiroko Tsurumi University, School of Dental Medicine, Assistant Professor, 歯学部, 講師 (50367306)
ASADA Yoshinobu Tsurumi University, School of Dental Medicine, Professor, 歯学部, 教授 (20184145)
TSUBOTA Kazuo Keio University, School of Medicine, Professor, 医学部, 教授 (40163878)
山田 耕一 鶴見大学, 歯学部, 助手 (60367307)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Autoimmune disease / Sjogren's syndrome / Linkage analysis / NFS / sld mice / 疾患関連遺伝子 |
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| Research Abstract |
NFS/sld murine model for primary Sjogren's syndrome (SS) reveals severe destructive autoimmune lesions developed in the salivary and lachrymal glands and these characterized phenotype is related with an autosomal recessive gene with sublingual gland differentiation arrest. NFS/sld mice and control C57BL/6 (B6) were mated to generate F1 mice following backcrossed with NFS/sld mice to generate N1 mice. When we analyzed the phenotype of N1 mice comparing with B6 mice, the frequency of sublingual gland differentiation arrest in N1 mice was highest score (61%). We selected three Mit markers from each chromosomes and are analyzing the size differences between NFS/sld mice and B6 mice by PCR. In addition, homeobox genes of the NK-2 class play key roles in pharyngeal development. Nkx2-3^<-/->mutant mice showed normal specification but delayed differentiation and abnormal morphogenesis of the sublingual glands. We analyzed the amount of the expressed Nkx2-3 gene and amino acid sequences. The result form real-time PCR analysis showed that the expression of Nkx2-3 was diminished in NFS/sld mice compare with B6 mice. This result indicated the possibility of defect of promoter region. We found a single nucleotide polymorphism (SNP) at 166 bp upstream of the start codon of the Nkx2-3 promoter. Moreover, we analyzed predicted CpG methylation in the promoter region. Variant methylation patterns at specific transcription-factor binding motifs within regulatory regions were no differences between NFS/sld and B6 mice. To investigate the possibility of mutated amino acid sequence and/or the expression of alternative splicing form of Nkx2-3, we analyzed genomic DNA sequence. We found a transversion causing substitution of glycine for baline in a exon region, but no alternative splicing form. These aberrant Nkx2-3 gene in NFS/sld mice might be a candidate of the Sjogren's syndrome disease related gene.
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