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Rat Chromosome (rat + chromosome)
Selected AbstractsA spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsyGENES, BRAIN AND BEHAVIOR, Issue 7 2009H. Suzuki The lde/lde rat is characterized by dwarfism, postnatal lethality, male hypogonadism, a high incidence of epilepsy and many vacuoles in the hippocampus and amygdala. We used a candidate approach to identify the gene responsible for the lde phenotype and assessed the susceptibility of lde/lde rats for audiogenic seizures. Following backcross breeding of lethal dwarfism with epilepsy (LDE) to Brown Norway rats, the lde/lde rats with an altered genetic background showed all pleiotropic phenotypes. The lde locus was mapped to a 1.5-Mbp region on rat chromosome 19 that included the latter half of the Wwox gene. Sequencing of the full-length Wwox transcript identified a 13-bp deletion in exon 9 in lde/lde rats. This mutation causes a frame shift, resulting in aberrant amino acid sequences at the C-terminal. Western blotting showed that both the full-length products of the Wwox gene and its isoform were present in normal testes and hippocampi, whereas both products were undetectable in the testes and hippocampi of lde/lde rats. Sound stimulation induced epileptic seizures in 95% of lde/lde rats, with starting as wild running (WR), sometimes progressing to tonic,clonic convulsions. Electroencephalogram (EEG) analysis showed interictal spikes, fast waves during WR and burst of spikes during clonic phases. The Wwox protein is expressed in the central nervous system (CNS), indicating that abnormal neuronal excitability in lde/lde rats may be because of a lack of Wwox function. The lde/lde rat is not only useful for understanding the multiple functions of Wwox but is also a unique model for studying the physiological function of Wwox in CNS. [source] Analysis of chromosome 10 aberrations in rat endometrial cancer,evidence for a tumor suppressor locus distal to Tp53INTERNATIONAL JOURNAL OF CANCER, Issue 7 2007Carola Nordlander Abstract We have recently shown in the BDII rat model of human endometrial adenocarcinoma (EAC), rat chromosome 10 (RNO10) is frequently involved in chromosomal aberrations. In the present study, we investigated the association between RNO10 deletions, allelic imbalance (AI) at RNO10q24 and Tp53 mutation in 27 rat EAC tumors. We detected chromosomal breakage accompanied by loss of proximal and/or gain of distal parts of RNO10 in approximately 2/3 of the tumors. This finding is suggestive of a tumor suppressor activity encoded from the proximal RNO10. Given the fact that Tp53 is located at RNO10q24-q25, we then performed Tp53 mutation analysis. However, we could not find a strong correlation between AI/deletions at RNO10q24 and Tp53 mutation. Instead, the observed patterns for AI, chromosomal breaks and deletions suggest that major selection was directed against a region located close to, but distal of Tp53. In different human malignancies a similar situation of AI at chromosome band 17p13.3 (HSA17p13.3) unassociated with TP53 mutation has been observed. Although RNO10 is largely homologous to HSA17, the conservation with respect to gene order among them is not extensive. We utilized publicly available draft DNA sequences to study intrachromosomal rearrangement during the divergence between HSA17 and RNO10. By using reciprocal comparison of rat and human genome data, we could substantially narrow down the candidate tumor suppressor region in rat from 3 Mb to a chromosomal segment of about 0.5 Mb in size. These results provide scientific groundwork for identification of the putative tumor suppressor gene(s) at 17p13.3 in human tumors. © 2006 Wiley-Liss, Inc. [source] Localization of the Gene Causing the Osteopetrotic Phenotype in the Incisors Absent (Ia) Rat on Chromosome 10q32.1,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2004Liesbeth van Wesenbeeck Abstract The incisors absent rat is an osteopetrotic animal model. Segregation analysis in 37 affected animals from an outcross enabled us to assign the disease causing gene to a 4.7-cM interval on rat chromosome 10q32.1. Further analysis of the genes mapped in this region will provide more insight into the underlying pathogenesis. Introduction: Many of the insights into the factors that regulate the differentiation and activation of osteoclasts are gained from different spontaneous and genetically induced osteopetrotic animal models. The osteopetrotic incisors absent (ia) rat exhibits a generalized skeletal sclerosis and a delay of tooth eruption. Although the ia rat has well been studied phenotypically, the genetic defect still remains unknown. Material and Methods: To map the ia locus, we outcrossed the inbred ia strain with the inbred strain Brown Norway. Intercrossing F1 animals produced the F2 generation. Thirty-one mutant F2 animals and six mutant F4 animals were available for segregation analysis. Results: Segregation analysis enabled us to assign the disease causing gene to rat chromosome 10q32.1. Homozygosity for the ia allele was obtained for two of the markers analyzed (D10Rat18 and D10Rat84). Key recombinations delineate a candidate region of 4.7 cM flanked by the markers D10Rat99 and D10Rat17. Conclusion: We have delineated a 4.7-cM region on rat chromosome 10q32.1 in which the gene responsible for the osteopetrotic phenotype of the ia rat is located. Although the sequence of this chromosomal region is not complete, over 140 known or putative genes have already been assigned to this region. Among these, several candidate genes with a putative role in osteoclast functioning can be identified. However, at this point, it cannot be excluded that one of the genes with a currently unknown function is involved in the pathogenesis of the ia rat. Further analysis of the genes mapped in this region will provide us more insight into the pathogenesis of this osteopetrotic animal model. [source] Genetic analysis of pancreatic duct hyperplasia in Otsuka Long,Evans Tokushima Fatty rats: Possible association with a region on rat chromosome 14 that includes the disrupted cholecystokinin-A receptor genePATHOLOGY INTERNATIONAL, Issue 3 2001Naohide Kanemoto An Otsuka Long,Evans Tokushima Fatty (OLETF) strain of rat spontaneously developed hyperglycemia, hyperinsulinemia, insulin resistance and mild obesity, which had been studied as animal model for type II diabetes mellitus (T2DM). Recently, we observed that this strain coincidentally developed atypical hyperplasia of the choledocho-pancreatic ductal epithelium with a complete incidence. In an effort to locate genes responsible for this hyperplasia, we prepared 288 backcross progeny from a mating between OLETF rats and BN rats (which do not develop hyperplasia), and performed a genome-wide scan using 207 polymorphic genetic markers. We observed a prominent association of hyperplasia with a region involving a marker locus D14Mit4 (P = 0.00020, Fisher's exact test) and Cckar (the cholecystokinin-A receptor gene; P = 0.00025, Fisher's exact test) which is known to be disrupted in an OLETF strain. Our findings indicated that epithelial hyperplasia of the choledocho-pancreatic duct is associated with a region on rat chromosome 14 around the Cckar gene in an additive fashion with another two susceptible loci, each on chromosome 9 and 7. This implied the possibility that Cckar deficiency could result in a predisposition towards pancreatic duct hyperplasia. [source] A Novel Renal Carcinoma Predisposing Gene of the Nihon Rat Maps on Chromosome 10CANCER SCIENCE, Issue 11 2001Okio Hino A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Spra-gue-Dawley (SD) strain in Japan, and named the "Nihon" rat in 2000. This study was designed to map the RC susceptibility gene in the Nihon rat using 113 backcross annuals. Our present data clearly show that the Nihon gene is genetically linked to interleukin-3 (IL3) gene (,2=93.6, Lod score=25.16), lethal (2) giant larvae (LLGL1) locus (,2=109.0, Lod score=31.56) and myosin heavy chain, embryonic skeletal muscle (MYHSE) gene (,2=90.6, Lod score=23.87), which are located on the distal part of rat chromosome 10. The order of the genes is the Eker (Tsc2) gene (located on the proximal part of rat chromosome 10; human chromosome 16p 13.3),21.3 cM,IL3 gene (human 5q23-31),4.4 cM,Nihon gene,0.9 cM,LLGL1 locus (human 17p11.2)-4.4 cM,MYHSE gene (human 17pl3.1). We also detected loss of the wild-type allele at the MYHSE locus, fitting Knudson's "two hit" model. Thus, the Nihon rat should have a mutation of a novel tumor suppressor gene related to renal carcinogenesis. [source] | ||||||||||