DBA Strain Research Articles

Periodicity of Wheel-Running Activity in Mice in Relation to Light-Dark Cycle; I. Strain and Age Differences

Male mice of 4 strains (C57BL/6, DBA/2, C3H/He, and I20/Se) were individually run for 24 hr in home cages with an activity wheel under normal (LD) and reversed (DL) conditions of light-dark cycle. LD condition was in light from 08 : 30 to 20 : 30, and DL condition was in light from 20 : 30 to 08 : 30, alternating with 12 hr of darkness in each condition. Brightness in the light period was about 330 lux. Each strain consisted of 4 groups (3, 5, 7, and 9 weeks of age at the beginning of the experiment) of 10 mice.As shown in Figures 1 and 2, the onset of the activities of mice in LD condition, as compared with those in DL condition, synchronized with their transition from light-on to light-off. Especially, those of the mice of DBA and I20 strains synchronized markedly. Moreover, it can be observed in the mice of all strains that transition from light-off to light-on in the time of night has a drifting effect on the onset of activity.Transformed data on the total activity for 24 hr shown in Table 1 were analyzed by 3-factorial analysis of variance. Significant values of F were obtained only in the main effects of strain (F=6. 314, df=3/288), conditions of light-dark cycle (F=13. 904, df=1/288), and age (F=3. 931, df=3/288). It can be observed from Table 2 that there are very clear differences among strains of mice in the alternation of the active and inactive periods synchronized with light-dark cycle. From these results it is suggested that the activities of DBA and I20 mice synchronize with light-dark cycle of both conditions, whereas the activities of C57BL and C3H mice do not so much synchronize with those conditions. The age-related activity changes could not be observed in the present study.We conclude from these results that the activity synchronizes with a light-dark cycle, and thus periodicity of the activity is achieved by onset response to light-off and drifting response to light-on. However, further researches are needed to determine whether the 24 hr-periodicity of activity is controlled either by light-dark cycle or by a circadian rhythmic clock.

Cross-fostering of DBA and C57Bl mice. Increase in voluntary consumption of alcohol by DBA weanlings.

Weanling mice of the alcohol-avoiding DBA strain cross-fostered to mothers of the alcohol-selecting C57Bl strain drank twice as much alcohol as did nonfostered DBA mice. In contrast, C57Bl mice cross-fostered to DBA mothers drank the same amount of alcohol as did nonfostered C57Bl mice. Differences in maternal behavior seem to be responsible for differences in alcohol selection by weanlings.

Genetic analysis of behavioural responses to novelty in mice.

To trace the genetic determinants of exploratory behaviour in house mice, I started a programme of selective breeding1. Using the F2 generation from a cross between the inbred strains C57BL/6J and DBA/2J as the foundation population, male mice were selected bidirectionally for frequency of exploratory rearing responses displayed in a novel environment. To transfer alleles responsible for high rearing scores from the C57BL strain to the DBA genetic background, selection was combined with repeated backcrossing to DBA females over five consecutive generations. A comparable procedure has been used by Chai2 for body size in mice. Since these early stages of the selection aimed at developing two lines of mice with similar genetic backgrounds, but differing for loci affecting rearing behaviour, no unselected control line was bred; the DBA strain could serve as this.

Evidence of a central cholinergic role in alcohol preference.

Specific genetic strains of mice which are alcohol preferrers and others which are alcohol non-preferrers have been differentiated. For example, the C57B1 strains have been shown to be alcohol preferrers and the DBA strains have been found to reject alcohol (Rodgers and McClearn, 1962). Thus far, the major biochemical differentiating factor between preferrer and non-preferrer strains has been in the rate of acetaldehyde metabolism where the DBA strains have been shown to metabolize acetaldehyde less rapidly and thus to show greater accumulation of acetaldehyde after ethanol ingestion with consequent greater associated signs of toxicity (Schlesinger et al., 1966). Other neurochemical parameters to differentiate the alcohol preferrers have been focused on the role of serotonin (5-HT). Alcohol selecting strain of rats have been shown to have a higher content of brain serotonin; chronic alcohol consumption further increases the brain content of serotonin in the alcohol preferrers but not in the non-preferrers (Ahtee and Eriksson, 1972). Para-chloro-phenylalanine (pCPA), a selective inhibitor of tryptophan hydroxylase, has been reported to reduce alcohol preference by some investigators (Myers and Veale, 1968) but not by others (Nachman et al., 1970).KeywordsBrain HomogenateBrain SerotoninCholine UptakeAlcohol PreferenceChronic Alcohol ConsumptionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Genotype-dependent electroencephalographic, behavioral and analgesic correlates of morphine: An analysis in normal mice and in mice with septal lesions

Electroencephalographic, locomotor, and analgesic responses were studied in two strains of inbred mice (C57BL/6J and DBA/2J) implanted with epidural cortical electrodes. For the C57 strain the injection of morphine produced a sharp increase of locomotor activity and the EEG showed high amplitude slow waves similar to sleep, while the same strain was less sensitive to the analgesic effects of the opiate. For the DBA strain the locomotor activity was not enhanced following morphine and there was no alteration of the EEG pattern, while a pronounced analgesic response was evident in this strain. Septal lesions antagonized morphine analgesia in both strains while locomotor and electroencephalographic responses were unaffected in C57 mice. The findings suggest the following. o (1) The electroencephalographic responses to morphine are genetically determined. (2) The septal area is implicated in morphine-induced analgesia but not in the locomotor responses or in the brain electrical responses to the opiate. (3) The electroencephalographic alterations induced by morphine do not seem to be directly connected with the analgesic properties of the drug.

Comparative Study of Acetylcholinesterase and Choline Acetyltransferase Enzyme Activity in Brain of DBA and C57 Mice

IN related mouse strains, some behavioural patterns, for example motor activity, aggression, sensitivity to audiogenic seizures and learning, seem to be genetically determined1–4. Bovet and Oliverio5,6 have shown that CBA, C3H and C57, strains score poorly on avoidance learning, in comparison to DBA and SEC strains with scores increasing with the purity of the strain.

Effects of intrahippocampal injections with methylscopolamine and neostigmine upon exploratory behaviour in two inbred mouse strains.

After stereotaxically injecting male mice of the inbred strains C57BL/6 and DBA/2 with two doses of methylscopolamine or with two doses of neostigmine into the left dorsal hippocampus, the frequencies of the exploratory acts rearing, leaning, and sniffing carried out in a novel environment were recorded. At the lower dose-level, the anticholinergic drug tended to augment exploration in strain DBA and to reduce it in strain C57BL; the two doses of anticholinesterase diminished the scores in both genotypes. From these data it is concluded that the hippocampus contains a cholinergic mechanism which regulates exploratory behaviour and which is genetically controlled.

Reductive metabolism of corticosterone in mice: differences in NADPH requirements of liver homogenates of males of two inbred strains.

The metabolism of 3H-corticosterone by C57BL/1OJ and DBA/2J mice has been studied in homogenates of liver from the two strains with and without the addition of a NADPH-generating system. A complete quantitative and structural analysis has been made of reduced metabolites produced by both strains, in the presence or absence of exogenous NADPH. These studies show that 3H-corticosterone is metabolized more efficiently to polar steroids in homogenates of the C57 strain and reveal a strong dependence upon exogenous NADPH for hepatic corticosterone metabolism in the DBA strain that is not apparent in C57. 3H-corticosterone is metabolized by both strains in vitro mainly to mixtures of products that are either reduced in ring A (tetrahydro-derivatives) or reduced both in ring A and at C-20 (hexahydro-derivatives). Among both tetrahydro- and hexahydro-derivatives 3β,5α metabolites predominate in both strains but 3β-reduction and C-20 reduction are markedly more active in the CS7 than in the DBA strain. In both str...

Cholesterol ester concentration and corticosterone production in adrenals of the C57BL-10 and DBA-2 strains in relation to adrenal lipid depletion.

During incubations in vitro for 2 hr in the presence of ACTH, adrenals of adult male C57BL/1OJ mice synthesized significantly more corticosterone from endogenous precursors than did adrenals of adult male DBA/2 J mice. Characteristically the amount of steroid produced by the latter strain fell during the second hour while that of the former continued to rise or remained constant. The concentration of cholesterol ester in the adrenal of the C57 was seven times as high as that of the DBA but unesterified cholesterol and triglyceride concentrations were the same in both. Histological studies with Sudan IV staining showed the adrenal cortex of the C57 to be lipidrich and that of the adult DBA to be lipid-poor. The adrenals of two strains known to carry the adrenal lipid depletion gene (ald) were shown to have cholesterol ester levels close to that of the DBA. There is a marked decline both in sudanophilia and in the cholesterol ester content of the adrenals at puberty in DBA mice but not in C57 mice. As in th...

Antigenicity of two established tumorogenic cell lines estimated by the migration inhibition test.

Summarya. MIT used in the present work was found to be a useful method for the evaluation of sensitization occurring in oncological experimental systems, where transplantation tests may fail due to high virulence of the tumor.b. Both cell lines used, L-1 and L-2c, which are established tumorogenic cell lines derived from the C3H strain, sensitize isogenic hosts when injected sc.c. No cross-reaction between the two cell lines could be demonstrated by the MIT as used in this work.d. Both cell lines sensitize hosts of DBA strain across H-2. However, only slight signs of cross-reaction were seen, when DBA spleen sensitized this way was challenged by C3H spleen cell homogenate.e. Experiments on tumors derived from the tumorogenic cell lines show cross-reactions with the original cell lines.f. Slight signs of autoimmunization were observed in C3H mice after sensitization by the transformed cell lines, when challenged by the normal C3H spleen homogenate.

Endocrine changes in two strains of mice exposed to constant illumination.

Female mice of DBA and C57 strains were exposed to constant illumination for 10 months and comparisons of the endocrine glands and secondary sex organs were made. As compared with ovaries of control mice, there was an increase of interstitium and cystic follicles and an absence of corpora lutea in those exposed to light. Tubular adenomas of the ovary were present in 2 mice. Endometrium was hyperplastic and the vagina markedly cornified. Degree of morphological changes in DBA mice exceeded that in C57 mice, suggesting that the ovaries of DBA mice are more responsive to illumination. (Endocrinology 86: 914, 1970)

Spontaneous calcification in hearts of DBA mice.

AbstractOnset, frequency and characteristics of the spontaneous calcification which occurs in hearts of mice of the DBA strain have been studied. Calcified myocardial lesions developed as early as 25 days of age. A limited inflammatory response was associated with the fine mineral granules of early lesions. With age, sites of calcium deposition became larger and agranular. There was no evidence of inflammation at such loci and adjacent connective tissue did not increase significantly. In the oldest animals (older than 90 days), fibrous encapsulation of calcified sites was typical. Calcareous epicarditis appeared by 30 days; was minimal (8%) through 90 days, and then rose sharply in incidence (50%) in older animals. Epicardial calcification was restricted to the right ventricle. In general the calcified lesions increased with age and were not related to sex. Incidence of all lesions was 17% by 30 days of age, 80% within 90 days, and 94% in mice older than 90 days.

Effects of reserpine on cardiac calcification in DBA mice.

The effect of daily injections of 0.1 mg/kg reserpine (Serpasil) on pathologic calcification of cardiac tissue in 12- to 16-month-old DBA strain mice was studied. After 3 weeks of daily injections, the tissue calcium levels were decreased significantly from control levels of 18.6 (atrial) to 13.2 and 20.1 (ventricular) to 12.8 meq Ca++/kg fat-free dry weight respectively. Histological observations also showed a decrease in spontaneous calcification of cardiac tissue in the reserpinized mice. Frequent findings in the calcified areas of the reserpine-treated mice were: less extensive calcification, a more granular appearance of the mineral, an associated inflammatory reaction, and adjacent areas of myocardial necrosis.

The effect of ingested arsenic on methylcholanthrene-induced skin tumors in mice.

Three strains of mice (C × C3H, DBA, and Balb/C) were selected on the basis of differing vigor or potentiaiity for cutaneous tumor development or both. These animals were fed arsenic trioxide in their drinking water in a concentration of 0.01%. Cutaneous tumors were initiated by the topical application of methylcholanthrene disks and promoted by transplantation. Although arsenic treatment appeared to increase the number of papillomas produced in the DBA strain, the effect was not statistically significant. The C × C3H mice, however, displayed an opposite effect, in that arsenic treatment resulted in a decrease in the number of papillomas produced. This effect was statistically significant with a P value < 0.05.

Fetal hemoglobin variants in mice.

Two strains of mice, DBA and C3H, have a fetal globin polypeptide chain which differs in electrophoretic mobility from the corresponding fetal chain of the C57B1 strain. Mice of the DBA and C3H strains also differ from those of the C57B1 in adult hemoglobin type. Results of backcrossing the (DBA x C57B1) hybrid to the C57B1 suggest that the fetal chain locus and the adult beta-chain locus are closely linked.

Tissue calcium levels, spontaneous and diet-induced cardiovascular lesions in mice *

Summary Spontaneous cardiovascular lesions developed in DBA mice and increased in incidence with age. Similar spontaneous lesions were absent in C mice. When both strains were fed a thrombogenic (atrial) diet the DBA mice showed a much greater incidence of cardiac damage. The atrial and ventricular calcium levels of normal DBA mice increased with age and were four times those in C mice. An increase of calcium with age did not occur in C mice. Calcium levels of these organs for both strains of mice paralleled the incidence of lesions observed. The higher calcium level was associated with the greater incidence of the lesions in the DBA strain.

Staining methods for calcium--a comparison based on reactions shown by cardiac calcinosis in DBA mice.

Spontaneous calcification, which occurs frequently in hearts of mice of the DBA strain, has been used to compare effectiveness of calcium stains. Three fixatives (1) 80% ethanol, (2) 10% formalin and 3.5% acetic acid in 95% ethanol (modified Lavdowsky's) and (3) a 1:1 mixture of concentrated formalin and absolute ethanol were tested for their subsequent effects on staining. Stains for Ca included purpurin, von Kossa's, phthalocyanin, and glyoxal bis(2-hydroxyanil). These, with appropriate counterstaining, were compared among each other, with hematoxylin-eosin (H-E), and with the periodic acid-Schiff (PAS) reaction. Fixatives (1) and (3) did not affect results appreciably, but the von Kossa technic was unsatisfactory after (2). All stain demonstrated sites of Ca deposits, but purpurin and von Kossa's gave greatest sharpness of definition and were the simplest to perform. H-E and PAS with Alcian blue showed the same Ca sites in addition to details of the surrounding tissue.

Saccharin reverses the effect of food deprivation upon fluid intake in mice

Hungry mice drank less when water was the only available fluid, but they drank more when a maximally preferred solution of saccharin was provided instead of water. The ingestion of saccharin did not ameliorate weight loss and appeared to serve no adaptive function. The saccharin effect was more pronounced in strain C57 BL 6 J than in strain DBA 2 J , which has a weaker preference for saccharin. During food deprivation saccharin preference scores rose in both strains. The correlation between changes in preference and changes in blood glucose was high during one period of food deprivation, but non-significant during a second period. There may be little causal relationship between these two variables. Taste can affect control mechanisms for fluid intake, thus reversing the usual decrease of drinking in food-deprived animals. We suggest that in such animals control of drinking a saccharin solution is shifted from a thirst motivation system to a hunger motivation system.

Body Protein and Fat, Blood Glucose and Free Fatty Acids in Various Strains of Mice

AbstractCarcass composition was determined in the NMRI, CBA, Swisse and DBA strains, and in NMRI X Swisse made obese by injection of goldthioglucose. Fasting for 24 hrs resulted in different degrees of weight loss depending on the strain. At the same time analysis of carcass composition revealed strain differences with regard to protein and fat. The changes of glucose and FFA in plasma after 24 hrs without food also varied among the strains.

Genetic Aspects of Resistance to Friend Leukemia Virus.

Resistance of inbred C57BL mice to Friend's leukemic agent has been documented in a number of studies(1,2,3). Analysis of F2 and backcross progeny from RF X C57BL crosses suggested that resistance is a simple recessive character (4). In an attempt to differentiate susceptibility in the CFW and DBA2 strains from C57BL-resistance by-standard mendelian methods, an alternate form of gene expression was suggested by our findings. These observations are described here.Materials and methods. Mice. C57BL/ Crgl and DBA2/Crgl mice were obtained from the Cancer Research Genetics Laboratory, University of California, Berkeley. Inbred CFW mice were obtained from the Lobund Laboratory, University of Notre Dame, Notre Dame, Ind. Virus. BALB/c-adapted Friend virus was obtained from Dr. W. Bostick, California College of Medicine, Los Angeles. It was specifically adapted to DBA and CFW mice by serial passage. After 7 passes in each respective strain, 2 pools of virus were prepared from spleen homogenates in the manner desc...