Strain-related Differences Research Articles

Acute and subchronic toxicity of the protease inhibitor N-alpha-tosyl-L-lysyl-chloromethylketone (TLCK) in mice.

The acute and subchronic toxicity in TLCK (N-alpha-tosyl-L-lysyl-chloromethylketone) was determined in mice using several different treatment regimens and several different strains of mice. The single dose LD50 was 59 mg/kg following intraperitoneal (ip) administration and was 64 mg/kg following subcutaneous administration to male Balb/c mice. When various doses (0,5,10,20,40 mg/kg) were administered ip to male Balb/c mice either two or three times per week for four weeks, mortality occurred in both regimens at the highest dose. Weight loss was recorded in all animals treated with 20 mg/kg. Histologic lesions in chronically treated mice were restricted to inflammation of the diaphragm and hepatic necrosis. No lesions were observed following administration of a single lethal dose. When TLCK was administered ip to males and females of 7 strains of mice, female NIH Swiss and female C57Bl/6 mice were more resistant. No other strain-related differences in sensitivity were noted.

The indole hallucinogens, N, N-dimethyltryptamine (DMT) and 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT), have different effects from mescaline on rat shuttlebox avoidance

The indole hallucinogenic drugs, N, N-dimethyltryptamine (DMT) and 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT), had a different psychopharmacological profile from mescaline on rat shuttlebox avoidance; the differences were strain and/or baseline-dependent. N, N-dimethyltryptamine and 5-MeO-DMT shared dose response disruptive effects with mescaline on avoidance behaviour in two rat strains who were performing the conditioned avoidance response at a high baseline (i.e. during acqusition in Fischer 344s—Experiment 1; on pretrained good performing hooded rats—Experiment 2). N, N-dimethyltryptamine and 5-MeO-DMT were without an effect when the baseline conditioned avoidance response was low (i.e. during acquisition in Zivic-Millers, Hoods or Roman Low Avoiders—Experiment 1; on pretrained poorly performing hooded rats—Experiment 2) but mescaline was facilitatory in these situations. There were strain-related differences in sensitivity to the drugs with Roman High Avoiders insensitive to DMT, 5-MeO-DMT and mescaline, while Fischer 344s were the most sensitive to these three drugs. The relative potency of these three hallucinogens in disrupting avoidance behavior (5-MeO-DMT > DMT > mescaline), in terms of mg/kg paralleled reports of their relative potency on central serotonergic activity. The facilitatory effect produced by mescaline, but not produced by DMT nor 5-MeO-DMT, may be related to the findings that mescaline has a stronger action on the catecholaminergic system than the indoles.

Age-dependent and strain-related differences of virulence of Semliki Forest virus in mice.

Factors that influence the virulence of Semliki Forest virus for mice have been studied. In vivo experiments showed that maximum brain infectivities following i.p. inoculation of adult mice with a virus strain of low virulence were less than those found in mice showing clinical signs in virulent infections. The virulent strains generally caused death before antibody could be detected in brain tissue; the less virulent strain caused an infection that was neuroinvasive, but infectivity increased less rapidly in the brain and allowed antibody to intervene before clinical signs were apparent. IgG3 antibody was first detected in brain tissue coincident with the beginning of the decline of brain infectivities in avirulent infections; other sub-classes of IgG antibody were not detected until later. In vitro experiments showed differences in abilities of SFV strains to replicate in tissue culture and adult mouse brain tissue, and differences in susceptibility to infection of brain tissue from mice of various ages. These in vitro results could provide a basis for differences of virulence.

DIFFERENTIAL TOXICITY OF CHLOROFORM IN THE MOUSE

This study helps to reaffirm that all individuals in a population do not respond similarly to environmental stimuli. Studies on individual differences in chloroform toxicity in mice have been reviewed, and these reports indicate that inbred strain-related differences within a species may help to point out the types of variability in response that one might encounter in studies on a genetically heterogeneous organism, like man. Statistics like median lethal or toxic dose in randomly bred animals may only serve to conceal the genetic variability that may exist. Two genetic variations in chloroform toxicity were described. In one, animals more sensitive to chloroform-induced death were shown to be more susceptible to renal toxicity; in the other, sensitive animals were unable to repair damaged renal tubules. Many other examples of genetic variation in response to foreign compounds have been reported. An absolute sex-related difference in regard to kidney damage, but not liver damage, that occurs on chloroform administration has been reviewed. Androgens play an integral role in modulating the sex-related difference and, possibly, the strain-related difference in sensitivity to kidney damage. It is interesting that tumors have been produced in experimental animals after long-term exposure to chloroform in the same organs that more » are affected by single doses of chloroform: hepatic tumors have been produced in mice, and renal tubular tumors have been found in male rats. The effects of long-term, low-level exposure to chloroform in man are largely unknown. However, occupational exposures as low as 10 parts per million in air have resulted in derangements in liver function; in rats, repeated maternal exposures to 30 parts per million chloroform in air have resulted in fetal growth retardation. Both of these effects occurred at exposures lower than the present occupational standard for humans. « less

Behavioral suppressant effects of clonidine in strains of normotensive and hypertensive rats

The behavioral effects of orally administered clonidine were investigated in Long—Evans (LE), Sprague—Dawley (SD) or Kyoto Wistar (KW) rats assumed to be normotensive and in NIH spontaneously hypertensive (SH)_ rats. Although clonidine (0.05–1 mg/kg) resulted in the same quanlitative effects, i.e., depression of motor activity, the dose of clonidine required to depress motor activity to 50% of control levels (ED 50) tended to vary according to strain. An analysis of variance of the dose response curves for the foru strains of rats indicated a significant strain effect. When the effects of clonidine on food-reinforced operant responding were investigated, it was observed that SD and SH rats differed with regard to rate and temporal patterning of IRT > 20 sec responding. Although oral administration of clonidine (0.006–.01 mg/kg) procedure similar percentage decreases from control in SH and SD rats, an analysis of the temporal patterning of responding indicated differences in responsiveness to the behavioral effects of clonidine. These studies demonstrate strain-related differences in responsiveness to the behavioral suppressant effects of clonidine. Marked between genetically hypertensive rats and rats assumed to be normotensive were not evident.

Comparison of the effects of d-amphetamine and lysergic acid diethylamide in two strains of rats having different behavioral baselines

Fisher ( F ) and Sprague Dawley ( SD ) rats were trained to press a lever on a fixed interval (FI) schedule of food reinforcement or to postpone electric footshock on an unsignaled, continuous avoidance schedule. F strain rats responded on the Fl schedule at a lower rate than the SD rats. Responding of F rats was increased by low doses (0.075–0.10 mg/kg, ip) of d -amphetamine that had no effect on SD rats. However, linear regression analysis of successive quartiles of FI responding indicated little difference between strains in terms of the rate-dependent effects of d -amphetamine (0.075–1.0 mg/kg, ip). In the continuous avoidance procedure, F strain rats had a baseline response rate that was almost twice that of SD rats. However, F strain rats were more sensitive than SD rats to the rate-increasing effects of d -amphetamine (0.1–1.0 mg/kg). Under both schedules of operant responding, SD rats appeared to be more sensitive than F rats to the effects of LSD (0.01-0.8 mg/kg, ip). Strain-related differences in sensitivity to the behavioral effects of d -amphetamine and LSD were not predicted from the observed differences in control baseline.

Age-related changes in the lipid metabolism of Fisher 344 rats.

Lipid metabolism of male Fisher 344 rats aged 2-24 months was studied. Serum and liver cholesterol levels did not display the age-related gradual increase seen in other rat strains. An increase in the serum plus liver cholesterol pool from 2 to 6 months was followed by a plateau through 18 months and then another increase at 24 months of age. The triglyceride pool increased from 2 to 6 months and then remained unchanged through 24 months of age. Cholesterol synthesis from acetate decreased 50% between 2 and 9 months and fell only slightly through 24 months of age. Assay of 3-hydroxy-3-methyl glutaryl Coenzyme A (HMG-CoA) reductase showed a similar pattern but did not decrease further after 9 months of age. Cholesterol 7alpha hydroxylase activity was not significantly altered by age. These age- and strain-related differences present an opportunity for a comparative study of the aging process using the parameters of lipid metabolism as indicators.

Strain-related differences in immunosuppressive effects of Enterobacteriaceae and their lipopolysaccharides on production in rabbits of antibody to enterobacterial common antigen.

Certain polysaccharides have been shown to inhibit the antibody response of rabbits to the common enterobacterial antigen (CA). The present investigation revealed that striking differences exist in the immunosuppressive effects of enteric bacteria and their lipolysaccharides (lps), depending upon CA production by the strains. Mixtures of immunogenic strains (Escherichia coli F2378 [R4], E. coli F470 [R1], or Shigella boydii F3140 [R]) and non-immunogenic CA-producing strains, such as E. coli O1, E. coli O113, Salmonella montevideo, and S. minnesota, as well as the R mutants E. coli F614 (R1), E. coli F757 (R1), and S. typhimurium his 642 (Ra), failed to elicit CA antibodies. In contrast, mixtures of the immunogen and CA-negative strains S. typhimurium his 386 (Ra) and S. minnesota P595 (Re) or R555 (Ra) yielded antibodies in titers similar to those elicited by the immunogen alone. Further, LPS of CA-positive but not of CA-negative strains exerted this immunosuppressive effect. Quantitative studies revealed that LPS of S. minnesota in amounts of 100 mug/ml was strongly immunosuppressive, in amounts of 20 mug/ml slightly effective, and in amounts of 4 mug/ml ineffective. It is postulated that hitherto unknown differences exist, either in composition or in configuration, between LPS obtained from different microorganisms to account for the strain-related differences in immunosuppressive effects and, further, that the immunosuppressive LPS interacts with immunogenic CA.

Mouse strain-related differences in the biologic and immunologic responses to a murine sarcoma virus.

Mouse strain-related differences in the biologic and immunologic responses to a murine sarcoma virus.

Variations in the interferogenic responses of two strains of mice.

Marked quantitative differences have been observed in the interferogenic responses of two murine strains. Inbred C57B1 mice exhibited a higher interferogenic response when induced with NDV or bacterial endotoxin than did random-bred Swiss mice, although the kinetics of interferon induction were essentially the same in both strains. When induced with tilorone hydrochloride, divinyl ether-maleic anhydride copolymer, or Statolon, random-bred Swiss mice consistently responded with greater interferon production than did C57B1 mice. While the studies reported here do not allow discrimination among several hypotheses that can be envisaged to account for these strain-related differences in the interferogenic responses, it is apparent that the magnitude of the interferon response is not only related to the genetic composition of the test animal, but is also tempered by the nature of the interferogen.

Differences in the constitution of antibody combining site in different mice strains.

AbstractAnti‐2,4‐dinitrophenyl (DNP) antibodies from nine different inbred mice strains were affinity labeled with four bromoacetyl derivatives of DNP haptens. Strain related differences in the number of combining sites labeled, as well as in the relative amount of labeled tyrosine and lysine were observed. Differences in the relative ratio of residues labeled did not change much with size of reagent and may be related to subpopulations of antibodies differing in the constitution of their combining sites.