Search PubMed⌕ Search

Biomedical subjects

T Serikawa

Publications and source records attributed to T Serikawa.

At least 91 records · Page 5Linked to original sources
PubMed1995

Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline.

The spontaneously diabetic BB rat is a well-established animal model of human insulin-dependent diabetes mellitus. Besides the lymphopenia gene (Iddm 1) and the MHC class-II genes of the RT1u haplotype (Iddm 2), at least one other non-MHC gene (Iddm 3) is considered essential for diabetes development. To investigate the participation of this third gene in the development of diabetes in our BB/OK rat subline, we analysed 119 [(BB/OK x DA)F1 x BB/OK] first backcross hybrids phenotypically and genotypically. Genotyping with 5 classical and 28 polymorphic microsatellite markers indicated that the third gene is located on chromosome 18, about 22 +/- 7 cM distal from the Olf locus (Iod score = 2.33). Significantly more diabetics than Iddm 1 and Iddm 2 homozygous nondiabetic subjects were homozygous for this locus. Interacting genes located on chromosomes X and/or 1 seem to be involved.

Animals↗
PubMed1994

Instability of microsatellites in rat colon tumors induced by heterocyclic amines.

Microsatellite instability in rat colon tumors induced by heterocyclic amines was examined by studies on the lengths of 85 microsatellite sequences, covering most of the rat chromosomes in tumors and normal tissues. Seven of eight colon tumors induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine showed alterations at least at one locus of microsatellite sequences, whereas no mutations were observed in colon tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Three 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced colon tumors had mutations in more than one microsatellite, their mutation rates being 2 of 85, 2 of 85, and 3 of 85 allele/mircrosatellite sequence, respectively. These data suggest that rat colon adenocarcinomas induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine but not 2-amino-3-methylimidazo[4,5-f] quinoline show a trait of microsatellite instability. This is the first systematic study of microsatellite instability in experimental animal models of carcinogenesis.

Animals↗
PubMed1994

Molecular cloning and chromosomal assignment of the mouse C-type natriuretic peptide (CNP) gene (Nppc): comparison with the human CNP gene (NPPC).

The mouse C-type natriuretic peptide (CNP) genomic fragment was isolated from a mouse genomic DNA library. The mouse CNP gene is composed of at least two exons and one intron. The 5'-flanking region contains an array of cis-acting regulatory elements and a dinucleotide CA repeat (microsatellite). Analysis of the deduced amino acid sequences revealed that mouse preproCNP is a 126-amino-acid peptide and that its C-terminal 22-residue peptide preceded by Lys-Lys is identical to porcine, rat, and human CNPs. On the basis of the polymerase chain reaction-analyzed microsatellite length polymorphisms among recombinant inbred strains of mice, the CNP gene (Nppc) was assigned to mouse chromosome 1. Furthermore, the human CNP 5'-flanking region was extended for sequencing, and comparison of the mouse and human CNP genomic sequences revealed regions of conservation and diversity. Using somatic hybrid cell methodology, the CNP gene (NPPC) was assigned to human chromosome 2. The present study has added another locus to the conserved syntenic group in mice and humans.

Amino Acid Sequence↗
PubMed1994

The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.

We identified the rat homolog to the human Wilson disease (WD) gene as the gene responsible for hepatitis (hts) in the Long Evans Cinnamon (LEC) rat. A genetic study using fifty-three backcross progenies showed that the rat WD gene detected by Southern blotting using the human WD gene as a probe was tightly linked to the hts phenotype of the LEC rat with no recombination. LEC is a transcriptionally deficient mutant because no transcript of the rat WD gene could be found in the LEC rat by Northern blotting. This rat WD gene was mapped to 16q12.23-12.3 by fluorescence in situ hybridization and mouse x rat somatic cell hybrid analysis.

Animals↗
PubMed1994

Tremor and zitter, causative mutant genes for epilepsy with spongiform encephalopathy in spontaneously epileptic rat (SER), are tightly linked to synaptobrevin-2 and prion protein genes, respectively.

Spontaneously epileptic rat (SER) is a homozygote for both tremor (tm) and zitter (zi) genes and exhibits epilepsy-like seizures and spongiform encephalopathy. Genetic linkage analyses revealed that the tm and zi loci were tightly linked to the synaptobrevin-2 (Syb2) on chromosome 10 and the prion protein (Prnp) on chromosome 3, respectively. The genomic DNA sequences of Syb2 of the tm/tm (TRM) rats and exon 2 of the Prnp of the zi/zi (ZI) rats were identical to those of a control rat strain WTC. In addition, no difference was detected for expression of the Syb2 and Prnp on the Northern blot analyses of TRM, ZI and WTC brain, suggesting that the Syb2 and Prnp genes are not the tm and zi, respectively. The assignments of tm and zi to rat chromosome 10q24 and 3q35, however, will be the first step towards the positional cloning of the genes.

Animals↗
PubMed1994

Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice.

The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.

Acoustic Stimulation↗
PubMed1994

Gene mapping of NMDA receptors and metabotropic glutamate receptors in the rat (Rattus norvegicus).

Five N-methyl-D-aspartate receptor subunit genes and six metabotropic glutamate receptor subtype genes have been assigned to particular rat chromosomes by using a rat x mouse somatic cell hybrid clone panel. N-Methyl-D-aspartate receptor subunit genes (gene symbol, GRIN) GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D have been assigned to chromosomes (Chr) 3, 10, 4, 10, and 1, respectively. Metabotropic glutamate receptor subtype genes (gene symbol, GRM) GRM1, GRM2, GRM3, GRM4, GRM5, and GRM6 have been assigned to Chr 1, 8, 4, 20, 1, and 10, respectively. In addition, GRIN2A and GRM6 loci were successfully localized on Chr 10 linkage maps by linkage analyses. The genetic distances between loci in cM (+/- SD) are as follows: GRIN2A-28.6(+/- 7.0)-RR24-23.3(+/- 6.4)-MYHSE, from a linkage analysis using the (SHR x WTC)F1 x WTC cross, and RR24-4.2(+/- 2.9)-GRM6-4.2(+/- 2.9)-MMYHSE-2.1(+/- 2.1)-ASGR, SHBG-27.1(+/- 6.4)-PPY, from a linkage analysis using the (ZI x TM)F1 x ZI cross.

Animals↗
PubMed1994

Wilson's disease gene is homologous to hts causing abnormal copper transport in Long-Evans cinnamon rats.

BACKGROUND/AIMS: The Long-Evans Cinnamon (LEC) mutant rat shows an excess copper accumulation in the liver and low serum ceruloplasmin activity. The disorder is controlled by a single autosomal recessive gene designated as hts. Wilson's disease is an autosomal recessive disorder of copper metabolism characterized by abnormal copper accumulation in the liver and low serum ceruloplasmin activity. The gene responsible for Wilson's disease has recently been isolated. The present study was designed to examine whether the LEC rat is an ideal animal model for Wilson's disease from a genetic point of view. METHODS: For chromosomal mapping of hts, genetic linkage analysis using rat microsatellite marker loci was performed. Furthermore, cosegregation between hts and a rat counterpart of the Wilson's disease gene was analyzed. RESULTS: hts was finely mapped to rat chromosome 16. Complete cosegregation between hts and a rat counterpart of the Wilson's disease gene was detected. CONCLUSIONS: hts is likely to correspond to a rat homologue of the Wilson's disease gene. The present results allow us to propose that the LEC rat is an ideal animal model for Wilson's disease.

Animals↗
PubMed1994

The alymphoplasia (aly) mutation co-segregates with the intercellular adhesion molecule-2 (lcam-2) on mouse chromosome 11.

A new spontaneous autosomal recessive mutation alymphoplasia (aly), which causes a systemic defect of lymph nodes and Peyer's patches, was mapped on mouse chromosome 11 by linkage analysis using (ALY x MSM)F1 x ALY backcross progeny (155 mice). The gene order and map distances on the chromosome were as follows (cM +/- SD); D11Mit14 (AntP91a), Krt-1 -(0.7 +/- 0.6)--D11Mit59--(1.9 +/- 1.1)--D11Mit52, D11Nds7 (Gfap)--(0.7 +/- 0.6)--aly, D11Mit10, D11Mit13 (Ace), D11Mit58 (Myla), lcam-2--(8.4 +/- 2.2)--D11Mit12. No recombinant was found among aly, D11Mit10, D11Mit13, D11Mit58 and lcam-2, suggesting the possible involvement of lcam-2 in the aly mutation. However, the nucleotide sequence of the lcam-2 gene of aly/aly mouse was identical to that of the control mouse. No difference was detected between aly/aly and the control mouse for expression of the gene by both Northern blot and reverse transcriptase polymerase chain reaction analyses. Furthermore, immunohistochemical analysis using a mAb revealed that the ICAM-2 protein was normally distributed in various tissues. These findings indicate that aly/aly mice do not suffer from defects of lcam-2. The four polymorphic microsatellite markers tightly linked with the aly gene will serve as admirable guideposts for a chromosomal walk to the aly gene.

Animals↗