Differences in kindling development in seven outbred and inbred rat strains

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague-Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.     

Open-field behavior in four inbred mouse strains.

Describes an objective, detailed analysis of the open-field behavior of 4 inbred strains of mice: A, BALB/C, C57BL/6, and DBA/2. During a 20-min period, 400 observations were made of the behavior of an S and scored into categories such as rearing, locomotion, grooming, sniffing at objects, freezing, etc. Significant differences between Ss of different strains were observed with regard to frequency of categories. The changes in frequency over time were strain-dependent for some behaviors. Some acts (e.g., rearing and grooming) occurred more frequently with the passage of time, whereas others changed little or decreased in frequency (e.g., sniffing at objects). The very infrequent occurrence of freezing behavior could not account for the large differences in activity between strains. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cryopreservation of mouse spermatozoa from inbred and F1 hybrid strains

Mouse epididymal spermatozoa from inbred(BALB/c, C3H/He, C57BL/6N, CBA/JN and DBA/2N) and F1 hybrid (B6C3F1, BDF1 and CDF1) strains suspended in cryopreservation solution (18% raffinose and 3% skim milk in distilled water) were frozen and stored at -196 degrees C. After thawing at room temperature, sperm motility and fertilizing ability were examined. Spermatozoa from all of the strains were successfully frozen, although the motility and the fertilization rates of frozen-thawed spermatozoa (the proportions of the fresh oocytes from Jcl:ICR strain which developed to pronuclear oocytes and 2-cell embryos after insemination by frozen-thawed spermatozoa) varied among strains (motility: 23% for C57BL/6N to 62% for DBA/2N; fertilization rates: 26% for C57BL/6N to 89% for DBA/2N). Nearly all 2-cell embryos fertilized by frozen-thawed spermatozoa were transferred to the oviducts of pseudopregnant recipients and 35-62% of 2-cell embryos developed into normal young.     

A study of oral morphine preference in inbred mouse strains

The generative potential of free perichondrial grafts from rabbit auricular and rib cartilage around a self-reinforced polyglycolic acid (SR-PGA) rod was examined in eight growing rabbits. A 15 x 15 mm perichondrial graft was dissected away from the posterior side of each auricular cartilage. One graft was wrapped around a 1.1 x 10 mm SR-PGA rod and the other served as a control and was shaped into a tube without an implant. Fifth rib cartilages were then resected subperichondrially on both sides. The remaining perichondrium on the other side was wrapped around a 1.1 x 10 mm SR-PGA rod, while the other served as a control and was shaped into a tube without an implant. All the grafts were placed inside pectoralis major muscles. Grafts were biopsied six weeks postoperatively. Neocartilage formation was seen in all grafts with one exception on both the implant and control sides. It formed a tube-like structure around the implant in four cases after grafting of auricular perichondrium and in three cases after grafting of rib perichondrium. New bone formation was also observed. SR-PGA implants did not seem to disturb the generative potential of perichondrium.     

An edited linkage map for the AXB and BXA recombinant inbred mouse strains

We have updated the history of the AXB and BXA recombinant inbred (RI) strains, typed additional loci, and edited the AXB, BXA RI database. Thirteen of the original 51 AXB and BXA RI strains are either extinct or genetically contaminated, leaving 33 living strains available from The Jackson Laboratory. However, we found a high degree of similarity among three sets of strains, indicating that these strains are not independent, which leaves 27 independent RI strains in the set. Accordingly, we modified the database by combining the AXB and BXA RI sets and eliminating strains that were genetically contaminated or extinct with no available DNA. We added 92 newly typed loci, retyped some questionable genotypings, and removed loci with excessive double crossovers or an insufficient number of typed strains. The edited strain distribution pattern (SDP) is available on the World Wide Web (WWW) (http://www. informatics.jax.org/riset.html) and now includes over 700 loci. Each locus is linked to adjacent loci with a LOD score of at least 3.0 with a few described exceptions. We also carried out a second editing designed for the analysis of quantitative trait loci by deleting extinct strains and loci with identical SDPs; this edited database is also available on the WWW.     

Ethanol-induced conditioned taste aversion in 15 inbred mouse strains.

This study used a genetic correlational strategy to characterize the neurobiological basis of ethanol's (0, 2, or 4 g/kg) aversive effects as indexed by conditioned taste aversion. Substantial strain differences in taste aversion and hypothermia were observed, but the genetic correlation between these phenotypes was not significant. However, significant genetic correlations were observed between taste aversion and ethanol-related behaviors measured in previous studies, including home-cage ethanol preference (r = .68) and ethanol withdrawal severity (r = -.69). Strains showing stronger taste aversion tended to show lower ethanol preference and higher withdrawal severity. This pattern of findings is consistent with previous studies suggesting a commonality in neurobiological mechanisms underlying these phenotypes. These results do not support the hypothesis that ethanol-induced taste aversion is mediated by the drug's rewarding properties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Daily variations in pineal melatonin concentrations in inbred and outbred mice

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS) were successively recorded in a 3-year-old girl with the acute hemiplegia syndrome. She was admitted to our hospital with complaints of fever, loss of consciousness and right side dominant clonic convulsions evolving into status epilepticus, and then recovered with sequelae of aphasia and right hemiparesis. Electroencephalography showed a generalized slow rhythm at the onset, and very low activities on the left hemisphere in the follow-up records. Brain CT and MRI revealed edema of the left hemisphere initially, followed by left side dominant brain atrophy. No cerebral vascular lesion was detected by magnetic resonance angiography. N-Isopropyl-[123I]-iodoamphetamine SPECT showed marked hypoperfusion of the left hemisphere accompanied by crossed cerebellar diaschisis. MRS at the initial stage detected decreased N-acetyl-aspartic acid and increased lactic acid signals in the bilateral hemisphere, which subsequently normalized only on the right side. These findings suggested brain damage and neural cell death in the left cerebral hemisphere, caused by acute encephalopathy. SPECT and MRS are useful new techniques to study the pathophysiology of the acute hemiplegia syndrome.     

Genetic resistance to urethan-induced pulmonary adenomas in SMXA recombinant inbred mouse strains

Development of pulmonary adenomas (PAs) in mice is under the genetic control of multiple host genes. We have established a new set of SMXA recombinant inbred strains from PA-susceptible A/J and PA-resistant SM/J mice. The number of urethan-induced PAs was variable among substrains of the SMXA recombinant inbred strains, indicating the involvement of multiple genes. SMXA24 mice were highly resistant to PA, although they had susceptible alleles at all four known susceptibility genes, including kras2 and MHC. To identify the resistance gene in SMXA24, progeny of reciprocal F1 crosses and progeny of backcrosses to A/J were given urethan at 4 weeks of age and examined for induced PA at the age of 5 months. In reciprocal F1 cross progeny, the incidence of PA was very low, indicating that the resistance was a semidominant trait. Quantitative trait analysis of the backcross generation revealed significant linkages to loci on chromosome 12 (logarithm of odds score, 6.47) and chromosome 11 (logarithm of odds score, 4.35). To date, two PA resistance (PAR) genes, Par1 (located on chromosome 11) and Par2 (located on chromosome 18), have been reported. From the map position, one of the resistance genes on chromosome 11 was indistinguishable from Par1. However, another resistance gene on chromosome 12 was new, and we named this gene Par3. A likely candidate gene for Par3 is nPKCn, which is expressed exclusively in skin and lung and is down-regulated in PA. Par1 and Par3 seemed to act synergistically.     

Genetic profile of the SMXA recombinant inbred mouse strains revealed with restriction landmark genomic scanning

We have applied the restriction landmark genomic scanning (RLGS) method to the SMXA recombinant inbred (RI) mouse strain set to reveal its detailed genetic profile. A total of 663 polymorphic RLGS spot loci were identified, 576 of which were assigned to chromosomes. Strain distribution patterns (SDPs) at 55 microsatellite marker loci were also obtained. As a result, the total number of loci with distinct SDPs on chromosomes increased to 400. These loci were dispersed on all chromosomes, except for the Chromosome (Chr) Y, and effectively covered the genome with an average spacing of 4 cM. The SMXA RI strain set, hereby, would be of value for genetic study.     

Genetic relation of life span to metabolic rate for inbred mouse strains and their hybrids

Average life spans were estimated for the male progeny from 21 of the 25 possible matings of 5 inbred mouse strains. Oxygen consumption was measured in an open system over a 48-hour interval. Resting metabolism, Mre, and average metabolism, Mav, were determined at 6-8 months of age, and at 24-34 months. Body weight, W, was determined at the time metabolism was measured. Life span, L, is negatively correlated with Mre and Mav, and positively correlated with W at both ages of measurement. This is in accord with the metabolic wear factor that had previously been established among 85 different species of mammals. A new metabolism variable, the energy partition coefficient, defined as the ratio of average to resting metabolic rate, Mav/Mre, has a parabolic relation to body weight, i.e., is maximal at an intermediate body size. The squared body weight deviation in turn has a negative correlation with life span. The correlation of L with Mav/Mre is positive, as expected, but not significant. These data suggest the existence of a longevity factor dependent on the partition of energy between the phasic metabolism of activity and the continuous maintenance metabolism.     

Relationship between phospholipid transfer protein activity and HDL level and size among inbred mouse strains

Site-directed mutagenesis was used to investigate the loading of iron into rat liver ferritin by ceruloplasmin. Changes were made in the H chain to investigate the role of tyrosines involved in an inherent ferroxidase activity thought to be involved in the self-loading of iron into ferritin. Mutation Y34F affected the rate of iron loading by ceruloplasmin and incorporation of the oxidized iron into the core. Mutation Y29R (making it analogous to the L chain) had no effect on iron oxidation but slightly decreased core formation. A double mutation in the L chain, to open the alpha-helix bundle channel, and R25Y, making the protein more analogous to the H chain, increased the amount of iron incorporated into the core, again suggesting that this Tyr is involved in ligand exchange for core formation. Additional changes in the L chain involving the BC loop suggest that the entire BC loop is involved in the association of ferritin with ceruloplasmin, increasing its ferroxidase activity and the rate of iron loading into ferritin.     

Fear conditioning in inbred mouse strains: An analysis of the time course of memory.

Three mouse strains were examined for short- and long-term memory for Pavlovian fear conditioning measured 1 hr and 24 hr after conditioning. Both DBA/2J and CBA/J mice exhibit reduced long-term memory for contextual fear conditioning compared with C57BL/6J mice. In cued fear conditioning, however, DBA/2J mice show reduced short- and long-term memory compared with C57BL/6J mice, whereas CBA/J mice exhibit reductions only in short-term memory. These results underscore the importance of examining the time course of memory retention, and they suggest that inbred mouse strains may provide a diversity of phenotypes. The results also suggest that the processes of short- and long-term memory storage as well as contextual and cued fear conditioning are dissociable and are mediated by genetically distinct neurobiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phenotypic patterns of distortion product otoacoustic emission in inbred and F1 hybrid hearing mouse strains

Distortion product otoacoustic emissions (DPOE) were obtained from five different hearing mouse groups: CBA/J, MOLF/Rk, ct (homozygous normal mice of the curly-tail stock), and the F1 hybrid offspring of the matings CBA/J x dn/dn and MOLF/Rk x dn/dn (dn/dn mice are the curly-tail stock with recessive deafness). The DPOE patterns of the CBA/J and ct strains were similar to each other and different from that of the MOLF/Rk. The two sets of F1 hybrid mice, (CBA/J x dn/dn)F1 and (MOLF/Rk x dn/dn)F1, were found to have significantly larger DPOE amplitudes than their hearing parent strains, MOLF/Rk and CBA/J, respectively. In addition, the DPOE amplitudes were greater for the offspring of the MOLF/Rk x dn/dn cross than for those of the CBA/J x dn/dn cross, even though they were lower for MOLF/Rk than for CBA/J. The distinct features of DPOE patterns among these five groups suggest that DPOE testing can be used for auditory phenotyping.     

Alcohol withdrawal severity in inbred mouse (Mus musculus) strains.

Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 ± 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of low-dose irradiation with x-rays and pi-mesons on embryos of two different mouse strains

The effects of two different kinds of radiation (X-rays and negative pions) on embryonic development of mice was examined. The application of a known radiosensitizer (lucanthone) combined with 13.5 rd whole-body irradiation on day 8 of gestation showed enhanced teratogenic action compared to treatment with each of the agents alone. The extent of intensification varied both with mouse strain and treatment, indicating possible differences in repair capacity and LET-dependency of sensitization effects. Strain differences were found in the incidence and type of chemical and radiation-induced malformations, which may be explained by different developmental stages at the time of treatment.