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PubMed1993

Interstrain differences in murine daunomycin-induced nephrosis.

Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DBA-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism.

Albuminuria↗
PubMedDate not supplied

Chemoimmunotherapeutical studies on Dalton's lymphoma with cis-platin.

Effect of cis-platin (cis-dichlorodiamine platinum II) on Dalton's lymphoma in syngeneic DBA and allogeneic Swiss white mice was studied. Normal healthy mice were immunized with cis-platin incubated cells and challenged to check the immunity developed. In vitro assay of cell mediated immunity was investigated by the capillary cell migration inhibition of reticuloendothelial cells from both DBA and Swiss white (treated as well as normal) mice against the specific tumor antigen. Cis-platin treatment results in specific enhancement of host cellular immune system.

Animals↗
PubMed1979

Genetic variability for regional brain gangliosides in five strains of young mice.

The quantitative and qualitative distributions of gangliosides were determined in the cerebrum, cerebellum, and brain stem of five inbred strains (C57BL/6J, DBA/2J, LG/J, C3H/HeJ, BALB/cJ) of mice at 21 days of age. Genetic differences were found among the strains for wet weight, absolute amount of gangliosides per region, and concentration of ganglioside (expressed on bolth a wet and a dry weight basis) in all three regions of the brain. The water content of the various brain regions showed the least amount of genetic variability. Coefficients of genetic determination were used to estimate the magnitude of genetic influence on these traits in each brain region. Significant differences were also found among the five strains for the distribution of certain gangliosides. The DBA strain, which is susceptible to audiogenic seizure at this age, had the highest level of the myelin-enriched ganglioside GM1 in all brain regions. Most of the genetic variation that influences the content and distribution of gangliosides among neurologically normal mice can be considered polygenic. Several possible sources of this genetic variation that may contribute to the differences observed among the strains are discussed.

Age Factors↗
PubMed1989

Place avoidance learning and stress-induced analgesia in the attacked mouse: role of endogenous opioids.

In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.

Animals↗
PubMed1985

Longterm effect of neonatal whole-body X-ray exposure on ploidy development in mouse liver cells.

Mice of the strains C3H, DBA, NZB, and NMRI were X-irradiated with 0.475 Gy and 2.85 Gy (or 3.80 Gy) at newborn stage or at the age of six months. Their livers were prepared at the age of one to maximum 18 months and the hepatocytes isolated. The DNA content of both whole cells and separated nuclei was measured by flow cytometry and the liver ploidy pattern was determined applying a correcting calculation. Irradiation with 0.475 Gy of newborns of strain C3H results in a relative decrease of octoploid cells and an increase of tetraploid nuclei during lifetime (significance level of 0.001). After irradiation with 3.80 Gy a reversed reaction was observed. However, if the animals were irradiated as adults with a dose of 3.80 Gy the 8c cells decreased significantly three months later. Similarly, newborns of the outbred strain NMRI irradiated with 2.85 Gy, showed an increase of octoploid cells from the third month on, but an oscillating pattern of the 4c nuclear DNA content. In strains DBA and NZB, significantly altered ploidy values could not be found, perhaps due to a too great variance of experimental values.

Age Factors↗
PubMed1994

Use of recombinant inbred strains for studying genetic determinants of responses to alcohol.

A recently-developed method of gene mapping is reviewed. Several responses to EtOH were studied with the purpose of identifying genes with modest effects (Quantitative Trait Loci, or QTLs). As an example, results from a study of acute ethanol withdrawal severity are discussed. Mice from inbred strains C57BL/6J and DBA/2J, and 19 of their Recombinant Inbred (BXD RI) strains, were given 4 g/kg EtOH and their acute withdrawal severity assessed with the handling-induced convulsion (HIC). HIC scores varied markedly among strains. Comparison of the pattern of strain means for withdrawal with a database comprising genotype of each BXD RI strain for almost 800 mapped polymorphic genetic markers revealed associations with several potential QTLs appearing on several mouse chromosomes. To verify the presence of a gene affecting withdrawal, we then withdrawal-tested individual F2 mice bred from the F1 cross of the parental C57 and DBA strains. These mice were then genotyped for several polymorphic markers close to a putative QTL on chromosome 2. Possession of the DBA allele in severely withdrawing F2 animals was significantly associated with one such marker, D2Mit9, confirming the presence of a gene nearby affecting withdrawal. As a further test, mice of the replicated Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) lines, selected for severity of EtOH withdrawal HIC, were also genotyped. Alleles at the D2Mit9 locus assorted disproportionately (and consistently) between the two pairs of WSP and WSR lines, while alleles at other loci did not. Thus, three tests consistently suggest the influence of a gene, tentatively termed Aw1, 37 cM from the centromere on chromosome 2, that appears to control as much as 40% of the genetic variance in withdrawal. The provisional locus is located very near to two candidate genes. Gad1 codes for the synthesis of glutamic acid decarboxylase, the rate-limiting enzyme for synthesis of GABA. A cluster of genes (Scn1, Scn2, Scn3) code for voltage-sensitive sodium channel proteins. These genes are plausible candidates for affecting withdrawal HIC.

Alleles↗
PubMed2004

Behavioural profiles of inbred mouse strains used as transgenic backgrounds. I: motor tests.

One of the characteristic manifestations in several neurodegenarative diseases is the loss of voluntary motor control and the development of involuntary movements. In order to determine the suitability of six mouse strains as transgenic background strains we investigated performance on a variety of tasks designed to identify subtle changes in motor control. On both the accelerating and the staggered speed rotarod all six mouse strains performed well. However, latency to fall from the rod was sensitive to both rotarod speed and repeated exposure to the apparatus. Performance of the DBA/2 mouse strain was highly variable across the time points used. On the acoustic startle test CBA mice showed the greatest degree of reactivity to the acoustic startle stimuli with both the C57 and DBA showing the least. Complex strain differences were also identified on measures of habituation to the startle stimuli and variations in the prepulse noise level, and prepulse/startle delay. Gait analysis using the footprint test did not reveal strain differences on measures of base width, overlap or stride length but the 129S2/Sv strain took significantly longer to traverse the runway than the other mouse strains. Finally, the swim tank test detected complex strain differences in swim speed, and the number of fore- and hindpaw paddles required to swim the length of the tank. These data taken together suggest that choice of background strain is a crucial consideration for the repeated behavioural assessment of motor deficits in transgenic mouse models of disease.

Acoustic Stimulation↗
PubMed1989

The role of control activity levels in the reported strain differences to the behavioral effects of drugs in mice.

The effect of d-amphetamine (3-100 mumoles/kg), scopolamine (0.3-100 mumoles/kg) and morphine (3-1000 mumoles/kg) were studied on the spontaneous motor activity (SMA) of four strains of mice: CF-1, DBA/2, C57BL/6 and CD-1. All three drugs increased the SMA of the CF-1, C57BL/6, and CD-1 strains at low to moderate doses and decreased SMA at higher doses. In the DBA/2 strain, d-amphetamine and scopolamine increased SMA at low doses and decreased SMA at high doses; only decreases in SMA were observed with morphine. When the drug effect was expressed relative to control levels of SMA, large apparent strain differences were shown to exist for all three drugs. In general, these strain differences were shown to exist for all three drugs. However, the majority of these strain differences could be attributed to the large differences which existed in the control level of SMA among the four strains. One important exception to this statement was shown to exist. The DBA strain responded differently (only decreases in SMA were observed) to morphine than did the other three strains. This decrease was not related to the control SMA level and could not be antagonized by naloxone (3 mumoles/kg, IP).

Animals↗
PubMed1990

Effects of the benzomorphan kappa-opiate, MR 2266 and its (+) enantiomer MR 2267, on thermonociceptive reactions in different strains of mice.

The effects of the benzomorphan kappa opiate MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in Swiss Webster, C57BL/6, BALB/c and DBA/2 strains of mice. In the hot plate (60 +/- 0.5 degrees C, cut-off time 120 s and tail immersion tests, MR 2266 (10 mg/kg, s.c., 15 min before) decreased, while MR 2267 (10 mg/kg s.c., 15 min before) increased the reaction latencies. In the hot plate test, the sensitivities for the effects of MR 2266 and MR 2267 on jump latency in different strains of mice were as follows: MR 2266; BALB greater than Swiss greater than C57BL greater than DBA and MR 2267; DBA greater than BALB = Swiss greater than C57BL. In the immersion test, for the hyperalgesic response of MR 2266, the rank order of strains was; BALB greater than C57BL and DBA greater than or equal to Swiss while the rank order for the analgesic effect of MR 2267 was; Swiss greater than DBA and BALB. The results indicate the presence of tonic kappa-receptor-mediated regulation of the spinal and supra-spinal thermonociceptive reactions which is stereospecific and strain dependent.

Animals↗
PubMed2004

The time of palatal fusion in mice: a factor of strain susceptibility to teratogens.

Induction of facial clefts in an animal model is often performed in experimental teratology. The susceptibility to teratogens of different strains of mice is genetically determined and seems to depend on the time of palatal fusion during embryogenesis. In order to elucidate the mode of action of preventive measures, we determined the exact time of palatal fusion in different strains of mice used for experiments in our laboratory. Fusion of the secondary palate is finished in the Halle: NMRI-mice at day 15, 0 h of gestation, in Halle: DBA and in A/WySnJ mice at day 15, 6 h and in the Halle: Jena AB-mice at day 15, 12 h. This sequence is at variance with spontaneous cleft rates and susceptibility to teratogens.

Abnormalities, Drug-Induced↗
PubMed2003

The effects of dietary restriction on humeral and mandibular bone in SENCAR, C57BL/6, and DBA/2 mice.

Dietary restriction (DR) increases the life span and retards the development of age-related disorders. However, the low body mass that accompanies DR is associated with risk factors for fracture that may outweigh the beneficial effects of DR on cellular aging that are mediated, in part, by limiting free radical generation and oxidative damage. We tested the effects of DR in murine models that differ in free radical generation capacity (SENCAR > C57 > DBA). Male mice of each strain were killed at 10 weeks of age (t(0); time zero) or randomized to an ad libitum-fed (AL-fed) or 30% DR feeding regimen for 6 months. The food consumption of AL-fed mice was measured daily. DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. The DR diet was normalized with respect to calcium (Ca), phosphorus (P), and micronutrients. Lean body mass (LBM), bone mineral density (BMD), and bone mineral content (BMC) in the humerus and mandible were determined by PIXImus densitometry. The length and midshaft width of the humerus were determined by direct measurement. There were highly strain- and diet/time-dependent effects on LBM, humerus length, mandibular and humeral BMD, and humeral BMC. The interaction between diet/time and strain was more significant in the humerus than the mandible. All 30% DR mice had lower humeral BMDs and BMCs than their respective AL-fed controls. However, 30% DR C57 and DBA (but not SENCAR) mice had higher humeral BMD and BMC than their respective t(0) controls. There was a linear relationship between LBM and humeral BMD and BMC in both AL-fed and 30% DR mice, suggesting that the lower BMD and BMC in 30% DR mice, relative to AL-fed controls, reflects a physiologic adaptation to lower biomechanical loading. Mandibular BMC in 30% DR C57 (but not DBA or SENCAR) mice was lower than that observed in their AL-fed controls. Mandibular BMD and BMC increased versus t(0) values in 30% DR mice of all strains.

Animals↗
PubMed1993

[Characteristics of the audiogenic convulsive crisis in mice made sensitive by magnesium deficiency].

Mice of the OF1, C57BL/6, AKR, C3H/He, DBA/2, BALB/C, B6D2F1 and CBA strains are susceptible to audiogenic seizures after 40 or 20 days of acute magnesium deficiency. The duration of the various phases of the audiogenic seizure response (at 100 dBA) (wild running latency period, convulsions latency period and the clonic and tonic convulsions) among these mice was measured. Using the Kruskall-Wallis test, no difference was recorded using these measurements and those obtained for genetically audio-susceptible animals. This shows that acute magnesium deficiency-induced audiogenic seizures develop in exactly the same way as in genetically audio-susceptible animals (21-days-old DBA/2 mice). Lower intensity (60 and 80 dBA) produced only audiogenic seizures in magnesium deficient mice. Repeated auditory stimulation caused an increase in the number of lethal seizures. Sound-induced seizures in magnesium deficient mice provide a sensitive screening test for anti convulsive drug, and for drugs use in magnesium depletion.

Acoustic Stimulation↗
PubMed2006

Stat1 deficiency exacerbates carditis but not arthritis during experimental lyme borreliosis.

Activation of the transcription factor Stat1 by interferon-gamma (IFN-gamma) is an important step in the development of antimicrobial effector mechanisms against many bacterial pathogens. Susceptibility to murine Lyme arthritis has been correlated with the production of several proinflammatory cytokines, especially IFN-gamma. To determine the role of IFN-mediated effector mechanisms in the development of Lyme borreliosis, we infected Stat1-deficient mice on both resistant (DBA), and susceptible (C3H) genetic backgrounds. Arthritis in Stat1(/) mice was similar to that of wild-type controls in both mouse strains. Spirochete loads in tissues were also unchanged in Stat1(/) mice. C3H Stat1(/) mice exhibited increased inflammation in the heart, whereas carditis was unchanged in DBA Stat1(/) mice. These results demonstrate that inhibition of macrophage activation and responses to IFN-gamma-mediated signaling do not alter the arthritis resistance or susceptibility phenotype; however, they do affect the severity of carditis in susceptible mouse strains.

Animals↗
PubMed1983

Strain-dependent modulation of memory by stress in mice.

The effects of immobilization stress were investigated in Swiss Webster (Swiss), DBA/2 (DBA), and C57BL/6 (C57) mice, tested in a passive avoidance situation. Retention performance was impaired in Swiss and DBA mice, and improved in C57 mice, immobilized immediately, but not 2 hr, after training. These effects lasted for less than 7 days in DBA and Swiss mice, while they were still present, in the C57 strain, 14 days after training. The naloxone antagonism of the effects observed was also demonstrated. The results are discussed in terms of the possible role of endogenous opioids, stress hormones, and genetic makeup in the stress-induced modulation of memory processes in the mouse.

Animals↗
PubMedDate not supplied

Water and electrolyte contents, cell pH, and membrane potential of primary cultures of astrocytes from DBA, C57, and SW mice.

Some basic properties of primary cultures of astrocytes derived from the cerebral cortex of an audiogenic seizure-sensitive strain of mice, DBA/2J (DBA), were studied with different approaches. The results were compared with those of audiogenic seizure-resistant strains, C57BL/6J (C57) and Swiss Webster (SW). Contents of intracellular water, protein, and DNA of DBA astrocytes were 0.673 +/- 0.019 ml/g cells, 0.082 +/- 0.006 g/g cells, and 0.0072 +/- 0.0005 g/g cells, respectively. These results are not different from those of either C57 or SW astrocytes. Intracellular concentration of K+, Na+, and Cl- ([K+]1, [Na+]1, and [Cl-]1) derived from the flame photometric and from the radioisotope uptake data of DBA astrocytes were 120.4 +/- 8.5, 25.9 +/- 3.2, and 26.8 +/- 1.8 mM/L cell H2O, respectively. [Na+]1 and [Cl-]1 in DBA astrocytes were lower than those in C57 and SW astrocytes. In DBA astrocytes, SITS decreased the cell/medium ratio (C/M) of 36Cl- and increased the C/M of 125I-; ouabain increased the C/M of 22Na+ and decreased the C/M of 125I-; bumetanide decreased the C/M of both 36Cl- and 22Na+; and NaClO4 decreased the C/M of 125I-. Similar results were observed in both C57 and SW astrocytes. Intracellular pH (pHi) as determined with 14C-DMO of astrocytes in HEPES-buffered saline solution averaged 7.04 +/- 0.03 for DBA, 7.01 +/- 0.02 for C57, and 6.97 +/- 0.02 for SW mice when pH of medium was maintained at 7.4. Modification of ion (HCO3-, Cl-, Na+, and K+) concentration and pH of culture medium all changed the pHi of astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1981

Ethanol-induced changes of dopaminergic function in three strains of mice characterized by a different population of opiate receptors.

The effects of ethanol have been studied in three strains of mice (DBA 2J, albino, and C57 BL/6J) having different populations of opiate receptors. Acute ethanol treatment induces a significant increase in striatal dopamine metabolism only in the mouse strains (C57 and albino) that are rich in enkephalinergic receptors upon nigrostriatal dopaminergic fibers. After chronic ethanol, the same strains develop tolerance to striatal dihydroxyphenylacetic acid increase, while the striatal dopaminergic recognition sites become supersensitive. DBA mice, which have lower numbers of enkephalinergic receptors and higher levels of enkephalins in the striatum, fail to show changes in central dopaminergic function after acute or chronic ethanol treatment. Our results indicate the importance of an interaction between ethanol and opiate receptors in determining the neurochemical and behavioral effects of ethanol.

Animals↗
PubMed1974

Immunological tolerance. Dissociation between in vivo and in vitro reactivity in parabiosed mice.

Although most mouse strain combinations succumb to a lethal wasting disease when parabiosed across a strong histocompatibility (H-2) barrier, a high proportion of DBA mice parabiosed to DBA/C3H F(1) hybrids survive and appear healthy. DBA mice accept C3H skin grafts following parabiosis, and may therefore be considered operationally tolerant of C3H antigens. Nonetheless, spleen cells from long-term DBA and F(1) parabionts give normal and enhanced responses, respectively, to C3H antigens in mixed lymphocyte culture (MLC). This indicates that the tolerance mechanism can distinguish between MLC recognition reactivity and in vivo effector reactivity, and that the former can therefore exist in the absence of the latter.

Animals↗