Osamu Koiwai
Shiga University of Medical Science
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Featured researches published by Osamu Koiwai.
The Lancet | 1995
Sachiko Aono; Hiroomi Keino; Y. Yamada; Yukihiko Adachi; T. Nanno; Eiichiro Uyama; Osamu Koiwai; Hiroshi Sato
Gilberts and Crigler-Najjar syndromes are characterised by unconjugated hyperbilirubinaemia due to complete and partial absence of bilirubin UDP-glucuronosyltransferase (UGT). Nucleotide sequences of the genes for bilirubin UGT were analysed in six patients with Gilberts syndrome. All patients had a missense mutation caused by a single nucleotide substitution and the mutations were heterozygous. In addition, relatives of patients with Crigler-Najjar syndrome types I and II, and of those with Gilberts syndrome were analysed. All ten relatives with mild hyperbilirubinaemia were heterozygotes with respect to each defective allele. These results suggest that Gilberts syndrome is inherited as a dominant trait.
International Hepatology Communications | 1996
Yukihiko Adachi; Toshinori Kamisako; Osamu Koiwai; Kazuo Yamamoto; Hiroshi Sato
Abstract Crigler-Najjar syndrome (types I and II) and Gilberts syndrome are familial disorders associated with severe to mild unconjugated hyperbilirubinemia. In these conditions, the activity of bilirubin UDP-glucuronosyltransferase (UGT1∗1), which is located in the hepatocyte endoplasmic reticulum, is defective, and severely and moderately decreased, respectively. UGT1∗1 is derived from one of the UGT1 genes. It has a promoter containing a TATA box and consists of exon 1A (which is one of the individual first exons) and common exons 2–5. UGT1∗1 mRNA is formed by differential splicing of these exons. In recent years, gene analysis of these syndromes has been carried out, and genetic abnormalities have been clarified. Homozygous nonsense mutations, mis-sense mutations, and other relevant mutations of exons 1A-5 have been reported in almost all of the patients with Crigler-Najjar syndrome type I, while mainly homozygous mis-sense mutations of exons 1A, 2, and 5 have been reported in type II patients. Almost all patients with this syndrome (types I and II) show autosomal recessive inheritance. On the other hand, some patients with Gilberts syndrome show heterozygous mis-sense mutations in exons 1A, 4, and 5, while others show homozygous 2-base pair-insertion mutation (TA) into the TATA box in the promoter region [A(TA)7TAA; normal: A(TA)6TAA]. The pattern of inheritance can be autosomal recessive or autosomal dominant. It has also been clarified that enzyme activity is lowered to about 30% (rather than 50%) by heterozygous mutations of the coding region, because of the occurrence of dominant negative mutation based on subunit-structure of the enzyme.
Gene | 1996
Yoshihiro Yasui; Kayo Hasada; Jian-Guo Yang; Osamu Koiwai
We have isolated a genomic clone encoding human selenoprotein P including the putative promoter region. The gene spans 12 kb and consists of five exons with a start codon in the second exon. A typical TATA sequence, the recognition motifs for a GATA-binding factor and the liver-specific factors, HNF-1 and HNF-3, were detected upstream from the transcription start point.
Journal of Human Genetics | 1995
Osamu Koiwai; Yoshihiro Yasui; Kayo Hasada; Sachiko Aono; Hiroshi Sato; Morihiko Fujikake; Tsugutoshi Aoki
Three Japanese patients with Crigler-Najjar syndrome type I carry an identical nonsense mutation in the gene for UDP-glucuronosyltransferase
Biochemical Genetics | 1992
Hiroshi Sato; Yuka Sakai; Osamu Koiwai; Tomomasa Watanabe
Restriction endonuclease fragment length variations (RFLVs) were detected by using a rat cDNA probe for the bilirubin UDP-glucuronosyltransferase (UDPGT) gene between two mouse strains, 129/Sv and MOL-MIT. RFLVs of the gene were found byEcoRI andPvuII digestions. From linkage analyses of the three-point cross test usingElo andEn-1 as marker genes, the bilirubin UDPGT gene was mapped at position 37 on chromosome 1. Bilirubin and phenol UDPGTs have been suggested to be expressed by a single gene by alternative splicing in human and rat. The mouse bilirubin UDPGT gene was namedGnt-1.
Journal of Human Genetics | 2014
Masahiro Suzuki; Marie Hirata; Miho Takagi; Taiichi Watanabe; Tomohiro Iguchi; Kotaro Koiwai; So Maezawa; Osamu Koiwai
Mutations in the gene encoding bilirubin UDP-glucuronosyltransferase (UGT1A1) are known to cause Crigler–Najjar syndrome type II (CN-II). We previously encountered a patient with a nonsense mutation (Q331X) on one allele and with no other mutations in the promoter region or other exons, and proposed that CN-II is inherited as a dominant trait due to the formation of a heterologous subunit structure comprised of the altered UGT1A1 gene product (UGT1A1-p.Q331X) and the intact UGT1A1. Here, we investigated the molecular basis of CN-II in this case by expressing UGT1A1-p.Q331X in cells. UGT1A1-p.Q331X overexpressed in Escherichia coli or mammalian cells directly bound or associated with intact UGT1A1 in vitro or in vivo, respectively. Intact UGT1A1 was observed as a dimer using atomic force microscopy. Fluorescent-tagged UGT1A1-p.Q331X and intact UGT1A1 were colocalized in 293T cells, and fluorescence recovery after photobleaching analysis showed that UGT1A1-p.Q331X was retained in the endoplasmic reticulum (ER) without rapid degradation. These findings support the idea that UGT1A1-p.Q331X and UGT1A1 form a dimer and provide an increased mechanistic understanding of CN-II.
Biochemical Genetics | 1995
Osamu Koiwai; Kayo Hasada; Yoshihiro Yasui; Yuka Sakai; Hiroshi Sato; Tomomasa Watanabe
The mouse gene for phenol UDP-glucuronosyltranferase (UDPGT;Ugtla1) was mapped at 42 cM on chromosome 1, a position identical to that of the gene for bilirubin UDPGT (Ugtla1), from linkage analysis of a three-point cross test withIdh-1, En-1, andUgtlal as marker genes. The cDNAs for mouse phenol and bilirubin UDPGTs, isolated after amplification by PCR, shared an identical 3′-half region. Our results strongly suggest that mouse bilirubin and phenol UDPGTs are expressed from a single gene and involve alternative splicing events. We also detected duplication of the gene for phenol UDPGT in all mouse strains examined with the exception of MOL-MIT and SUB-SHH.
Biochemical and Biophysical Research Communications | 1993
Sachiko Aono; Yasukazu Yamada; H. Keino; N. Hanada; T. Nakagawa; Y. Sasaoka; T. Yazawa; Hiroshi Sato; Osamu Koiwai
Human Molecular Genetics | 1995
Osamu Koiwai; Miwako Nishizawa; Kayo Hasada; Sachiko Aono; Yukihiko Adachi; Naoto Mamlya; Hiroshi Sato
Pediatric Research | 1994
Sachiko Aono; Yasukazu Yamada; Hiroomi Keino; Yoshiko Sasaoka; Tsuneo Nakagawa; Shoju Onishi; Shunji Mimura; Osamu Koiwai; Hiroshi Sato