A rat genetic linkage map and comparative maps for mouse or human homologous rat genes

Yamada, Junzo; Kuramoto, Takashi; Serikawa, Tadao

doi:10.1007/bf00292332

Cited by 205 publications

(88 citation statements)

References 192 publications

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“…According to the recent review, as many as five additional loci have been associated with seizure predisposition in EL mice (30). The Ell location in mouse chromosome 9 is syntenic with human chromosome 3 and rat chromosome 8, and the El2 region in mouse chromosome 2 with human chromosome 20 and rat chromosome 3 (13). In rats, polymorphic genetic markers and the genetic linkage map have been extensively improved by rat geneticists, including our group (14, 3 1).…”

Section: Corneal Electrodesmentioning

confidence: 99%

NER Rat Strain: A New Type of Genetic Model in Epilepsy Research

Noda¹,

Hashizume

Maihara

et al. 1998

Epilepsia

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Summary:Purpose: We characterized and evaluated as an animal model of epilepsy NER, a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj:Wistar.Methods: Animals were monitored through the inbreeding course, and video-EEGs were recorded selectively. External seizure-provoking stimuli were applied to NER and to a control parental strain. FI, F2, and backcross progenies were produced between NER and a nonepileptic unrelated strain. Pathologic study included hematoxylin-and-eosin (HE), Kliiver-Barrera's, modified Bodian silver, and neo-Timm's staining.Results: After the F9 generation, 94%-98% of NER exhibited spontaneous tonic-clonic convulsions, beginning with neck and forelimb clonus, wild jumpinghnning, opisthotonic posturing, and evolving to tonic, then clonic convulsion, followed by postictal flaccidity. Most seizure onsets occurred between 2 4 months of age, and the incidence was 0.45 k 0.21 seizures in 12 h. Ictal cortical and hippocampal EEGs were characterized by high-voltage spikes followed by diffuse spike-andwave or polyspike-and-wave complexes. NER revealed seizure susceptibility to pentylenetetrazol, tossing, and transcorneal electroshock, but not to tactile, photic, or acoustic stimuli, or to transauricular electroshock. Mating experiments revealed that 0% (0146) of the animals in F1,25.5% (1315 1) in F2, and 63.6%(56/88) in backcross progenies exhibited spontaneous tonicclonic convulsions without sex difference. For all these epileptic traits, no pathologic changes were demonstrated in the CNS.Conclusions: NER frequently exhibited spontaneous convulsions, controlled by a major autosomal recessive gene for epilepsy, that are comparable to generalized tonic-clonic seizures in humans. This can serve as a new genetic model in epilepsy research.

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Section: Corneal Electrodesmentioning

confidence: 99%

NER Rat Strain: A New Type of Genetic Model in Epilepsy Research

Noda¹,

Hashizume

Maihara

et al. 1998

Epilepsia

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“…Furthermore, the human chromosomal region homologous to the rat genomic interval for the chromosome 20 QTL is 6p21 [1,4,14]. This comparative map suggests the glucagon-like peptide-1 receptor (GLP-1R) locus [10] as positional candidate gene, which is physiologically involved in β-cell function.…”

mentioning

confidence: 99%

Identification of a Quantitative Trait Locus Influencing Plasma Insulin Levels after 70% Pancreatectomy Using the OLETF Rat.

Moralejo

Ogino

Zhu

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat has poor capacity for proliferation of pancreatic β-cells after partial pancreatectomy, which may be the critical pathogenetic event in NIDDM development. The poor pancreatic β-cell proliferation in this model is characterized by reduction in β-cell mass and decrease in insulin content in the remnant pancreas. Our investigation was designed to identify quantitative trait loci (QTLs) responsible for β-cell mass and plasma insulin levels after partial pancreatectomy by performing a genome-wide scan in an F 2 intercross obtained by mating the OLETF and the Fischer-344 (F344) rats. We have identified a suggestive QTL for the plasma insulin levels, near D20Mgh5 on rat chromosome 20, with a maximum lod score of 3.75 which accounts for 20% of the total variance, while no QTLs were detected for β-cell mass. This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than β-cell proliferation. -KEY WORDS: NIDDM, OLETF rat, QTL.J. Vet. Med. Sci. 60(10): 1157-1160, 1998 Hirashima and Kawano, and inbred Fischer-344 (F344) rats were obtained from Charles River Japan, Inc. (Yokohama, Japan). We arranged crosses between female OLETF and male F344 rats to produce 98 male F 2 progeny. Only male rats at 6 weeks of age at the beginning of the study were subjected to 70% pancreatectomy for genetic studies. After an overnight fast, animals were anesthetized with ether and given additional ether if needed during surgery. All pancreatic tissue was removed by gentle abrasion with cotton applicators, except for an anatomically well-defined remnant bordered by the branch of the hepatic portal vein and the first portion of the duodenal loop. After surgery, the rats had food and water available ad libitum. Nonfasting plasma insulin concentrations were measured at 28 days after surgery. Blood samples were obtained by tail snipping, and non-fasting insulin concentrations in the plasma were determined by a commercially available kit (Eiken Kagaku, Tokyo, Japan) based on radioimmunoassay with rat insulin (Novo, Bagsvared, Denmark) as a standard. Pancreas was excised and cleared of extraneous lymph nodes and fat at 28 days after surgery. The pancreas was weighed and cassetted with the same anatomic orientation, placed in Bouin's fixative, and processed for paraffin embedding using a standard protocol. For the measurement of β-cell mass, two sets of three serial sections (3-5 µm thick) were obtained at intervals of ~250 mm. The sections were first deparaffined and then immunostained for insulin by using ABC kit (Amersham, UK). The primary antibody used was polyclonal guinea pig anti-porcine insulin antibody (1:400, Dako Carpinteria). Using Weibel's point-counting morphometrics [13], the relative volume of β-cells was quantitated at 200 × magnification using a 9...

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“…E12, one of the epilepsy-related loci for EL mice, is located on mouse chromosome 2 (35)(36)(37), which has been shown to be orthologous to rat chromosome 3 by comparative mapping studies (19,20). For this reason, PCR primer pairs for mice were used in our current study as genetic markers in linkage analysis on rat chromosome 3.…”

Section: Discussionmentioning

confidence: 99%

“…Table 1 lists the 119 SSLP markers (109 for rats and 10 for mice) applied to group I, and the association of seizure susceptibility with cach marker. SSLP markers on mouse chromosome 2 were used for linkage analysis on rat chromosome 3 because the two proved to be orthologs (19,20). Among 125 primer pairs of mouse chromosome 2, 34 yielded specific PCR products using rat DNA templates.…”

Section: Linkage Analysismentioning

confidence: 99%

Chromosomal Mapping of Genes for Epilepsy in NER: A Rat Strain with Tonic‐Clonic Seizures

Maihara¹,

Noda²,

Yamazoe³

et al. 2000

Epilepsia

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Summary:Purpose: NER is a mutant rat strain that exhibits spontancous tonic-clonic convulsions accompanied by epileptic discharges on ictal EEG and serves a s a model for generalized tonic-chic seizures in humans. Our previous experiments have suggested that a major autosomal rccessive gene and several minor genes regulate the inheritance of tonic-chic seizures in NER. The purpose of this study was to confirm the mode of inheritance and to locate the causative genes for epilepsy in NER on the rat genetic map.Methodx We developed F 1 hybrid (F 1) and reciprocal backcross progenics of NER with a seizure-resistant strain, F344, and evaluated their seizure susceptibility under tossingstimulatcd and nonstimulated conditions. Backcross animals were genotyped using simple sequence length polymorphism markers for polymerase chain reactions. Linkage between seizure susceptibility and marker loci was analyzed by x2 statistic tests and by the computer programs MAPMAKER/EXP and MAPM AKER/QTL.Results: Under tossing-stimulating conditions, tonic-clonic scizures were provoked in 90% of NER and 66% of (FI x nimals, but no seizures occurred in the F344, FI, or (F1 x F344) backcross animals. Routine monitoring of nonstimulated animals revealed spontaneous tonic-chic convulsions in 100% of NER and 64.2% of (FI x NER) backcross animals, but no seizures in F344 or F1. Gender effect on seizure susceptibility was negligible in (F1 x NER) backcross in both conditions. Preliminary genome-widc scanning and subscquent precise location of the causative genes revealed seizure susceptibility loci, designated Nerl and Ner2, on rat chromosomes I and 3, respectively.Conclusions: Nerl is a locus that controls the inheritance of spontaneous tonic-clonic seizures in an autosomal recessive mode, whereas Ner2 affects the Occurrence of tossing-induced seizures. Orthologous genes in the vicinity of these loci may be related to epileptogenesis in other species, including humans.

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A rat genetic linkage map and comparative maps for mouse or human homologous rat genes

Cited by 205 publications

References 192 publications

NER Rat Strain: A New Type of Genetic Model in Epilepsy Research

NER Rat Strain: A New Type of Genetic Model in Epilepsy Research

Identification of a Quantitative Trait Locus Influencing Plasma Insulin Levels after 70% Pancreatectomy Using the OLETF Rat.

Chromosomal Mapping of Genes for Epilepsy in NER: A Rat Strain with Tonic‐Clonic Seizures

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