Circadian variation in concentrations of testosterone in the plasma of male mice: a difference between BALB/cBy and C57BL/6By inbred strains.

Diurnal variations in testosterone in plasma were studied in two inbred strains of mice, BALB/cBy and C57BL/6By. Blood was taken every 4 h over 24 h from male mice at 70 days of age using a lighting regimen of 12 h light t 12 h darkness (lights on 07.00-19.00 h). Values of testosterone in plasma were transformed to log(testosterone in ng/ml) to reduce inequality of variance between groups. In both strains, the distribution of pooled values over all times of day was bimodal, and bimodality was present at most times of day. Circadian variation was evaluated by dividing the transformed values into high and low modes at each time of day and testing for significant variation in the number of animals in each mode over time using the chi-squared test. Significant circadian variation was found in the BALB/cBy strain of mice but not in the C57BL/6By strain. The highest number of high mode cases for BALB/cBy mice was at 22.00 h and the lowest number of high mode cases was at 10.00 h. The log transformation and bimodality of these values are presented as biological expressions of blood levels of testosterone and of tissue responses to these levels in the male mouse. The strain difference in circadian variation may be related to reported circadian changes in behaviour and to possible genetic effects on sensitivity to environmental change or capacity to express circadian rhythms.

Multivariate and behavior genetic analysis of avoidance of complex visual stimuli and activity in recombinant inbred strains of mice.

Sixty-six mice of 11 genetic stocks (the Bailey recombinant inbred strains CXBD, CXBE, CXBG, CXBH, CXBI, CXBJ, CXBK; their progenitor strains, BALB/cBy and C57BL/6By: and the reciprocal hybrids, B6CF and CB6F) were tested in a two-compartment apparatus and in a shuttlebox, with five measures taken relating to activity and to approaches to novel and complex stimuli. A factor analysis of these measures revealed two factors, the first involving behavior relating to novel stimuli and the second relating to locomotor activity. In a second experiment, 132 mice of the same strains were tested on four of the measures used previously. On the two measures which had high loadings on the first factor and very low loadings on the second, it was possible to determine a strain distribution pattern (SDP), with the same SDP being found for both measures. When confirmed by testing mice from two congenic histocompatibility strains H(w54) and H(w80), we were able to determine that avoidance of novel/complex stimuli (neophobia) is controlled by a gene or genes at chromosomal segments H-24c and H-1b. It was also found that a polygenic model is consistent with behavior measured by the second (activity) factor.

Morphine analgesia in mice of different ages.

The analgesic response to 5 mg per kg morphine sulfate was examined in male C57BL/6J mice aged from 2 months to 28 months by the tail-flick assay. The baseline latency of old mice was slightly lower than that of young mice. There was a smaller increase in latency after morphine in old mice than in young mice. Decreased analgesic response in old mice was accompanied by a slower rate of uptake of labeled morphine into the blood after i.p. injection and a longer half-life of the drug. There was no difference between young and old mice in the number of narcotic receptors in the brain.

Some methodological problems in age comparisons of EEG sleep patterns for C57BL/6J mice.

Some methodological problems encountered in age comparisons of EEG patterns are discussed in the context of an analysis of open field activity scores before and after preparation for, and recording of EEG sleep patterns. Plasma corticosterone levels 11 days after surgery for EEG electrode implantation were also measured. Activity levels were modified more for three older than for a younger group of animals following surgery/recording sessions. Corticosterone levels were appreciably elevated for the oldest group of animals. The possibility was raised that procedures designed to allow recovery from post surgical shock and adaptation to electrode connections may result in disproportionate differences across age groups.

Regional brain catechol-O-methyl transferase: age related differences in the mouse.

Activity levels of COMT were measured in the frontal cortex, hippocampus, hypothalamus and amygdala of two strains of male mice, C57BL/6J and DBA/2J, at various ages between 2 and 30 months. Determinations were made in mice housed under normal conditions and in mice exposed to a form of mild stress, an open-field apparatus, for 5 minutes. There were no major significant differences between the two strains as a function of age. However, after the open-field experience, C57BL/6J mice appeared significantly more responsive to the environment, as interpreted by increases in COMT, than DBA/2J mice. Interpretation is offered that C57BL/6J mice possess a more labile norepinephrine system, in spite of aging, than DBA/2J mice.

Cortex weight: a genetic analysis in the mouse.

Differences in forebrain weight, forebrain weight/body weight ratios, and body weight were examined for the RI strains, their progenitor strains, and reciprocal F1 hybrids. The experiment was done in two widely separated laboratories with identical procedures for feeding, watering, and removal of brain tissue. The resulting strain distribution patterns suggested the influence of two or more loci in each laboratory. However, brain weights differed in the two laboratories. Some of the strains examined exhibited increased weights for the variables under consideration, while others exhibited decreased weights or no change at all. Implications for generalizations drawn from observations obtained in any single laboratory were discussed.

Changes with age in protein-bound iodine (PBI) and body temperature in the mouse.

Protein-bound iodine (PBI), body temperature, and the response of the thyroid gland to different doses of thyrotropin (TSH) were examined in males of two inbred strains of mice at different ages. Results indicate persistent decline in PBI with advancing age that is significantly greater in DBA/2J than C57BL/6J mice. The magnitude of the PBI response to TSH diminishes in both strains with advancing age but is significantly greater in strain DBA/2J than C57BL/6J. Body temperature was found to decline with advancing age and was highly correlated with thyroid function. Although additional research is needed, a tentative conclusion is that advancing age imparts a diminished response of the thyroid gland to endogenous thyrotropin. This is the first report of age-related changes and particularly correlation between PBI and body temperature in genetically controlled mouse strains. The indications are that such thyroid-temperature relationships are genotype dependent.

Genetic analysis of water maze discrimination learning for Mus musculus: polygenes and albinism.

Recombinant inbred strains, their progenitor strains and reciprocal F1 hybrids were given thirty spatial discrimination learning trials in the water maze. The pattern of RI strains in relation to the reciprocal F1 hybrids and the progenitor strains, and differences among strains, suggested that different sets of genes affect the various components of water maze discrimination learning. There was no evidence that the albino gene influenced either inferior or superior performance. Pigmented strains performed as well as, or better than, some albino strains, and albino strain BALB/cBy differed significantly from albino strains CXBG and CXBI. The two reciprocal F1 hybrids differed from blocks 2 and 3 of discrimination trials when swimming time was used a dependent variable. Thus, it appears that performance of the F1 hybrids was influenced by paternal effects, maternal effects, or paternal maternal interactions.

Morphine sensitivity and tolerance: a genetic investigation in the mouse.

Sensitivity and tolerance to morphine were determined in 2 strains of mice, BALB/cBy and C57BL/6By, their reciprocal F1 hybrids and seven of their recombinant inbred strains. Sensitivity was established based on locomotor activity following the administration of saline, 10 or 20 mg/kg of morphine hydrochloride while tolerance was established according to the "hot plate" method following the single or repeated administration of saline, 5, 10, or 20 mg/kg of morphine hydrochloride. Results indicate that both sensitivity and tolerance to morphine are genotype-dependent and their inheritance is characterized by dominance or partical dominance. Further clarification of the genetic relationship of sensitivity, tolerance and analgesia to morphine must await analysis of the brain morphine-binding protein currently being conducted.

A genetic analysis of the response to morphine in mice: analgesia and running.

Two progenitor strains, BALB/cBy and C57BL/6By, their reciprocal F1 hybrids, and seven of their recombinant-inbred derived lines were used to examine the genetic basis of the response to thermal pain, and morphine analgesia at doses of 2.5, 5.0 and 10.0mg/kg. Both the latency of response to thermal pain and the analgesic response differed significantly among the various strains tested. Strong genetic determinants appear to control their responses. Analyses of the data did not permit clarification regarding the linkage of these determinants. Photoelectric activity cages were used to test the running response of the same strains to 12.5, 25 and 40 mg/kg morphine sulfate. The genetic determinants for running activity were different from those for analgesia. There is clear evidence for two or more loci controlling the behavior at 60 and 75 min after injection, but not enough information to define the loci involved.

Electroencephalographic changes with age in male mice.

Electroencephalographic (EEG) changes, as measured by the awake state, slow-wave sleep (SWS), rapid-eye movement (REM) patterns and ratio of REM/total sleep, were recorded in aging male mice of DBA/2J and C57BL/6J strains. Results indicate that there is a significant increase in the awake state accompanied by significant decrease in SWS with advancing age for both strains, although these changes appear more pronounced in DBA/2J mice than C57BL/6J mice. Of considerable significance is the finding that REM sleep is absent in mice of DBA/2J strain at 23.5 months of age. Based on these findings, the conclusion was reached that strain DBA/2J ages significantly faster than C57BL/6J. The difference in aging between the two strains emphasizes the need for additional studies dealing with genetic aspects of aging.

Dominance behavior: a phylogenetic analysis in the mouse.

Tube-dominance behavior differed significantly in C57BL/6By and BALB/cBy mice. Evaluation of these two inbred strains, and their recently developed recombinant inbred strains permitted the derivation of an hypothesis regarding possible genetic control of this behavior in mice. The results were analyzed by means of patristic matrices with accompanying phylogenetic tree analysis that marks the first occasion that such analysis has been used for a behavioral trait. Based on the data obtained and the statistical analyses and groupings of the various strains, the most satisfactory hypothesis that can be proposed at this time is one which assumes that dominance behavior, as measured in this experiment, is influenced genetically by at least 3 loci. Attempts to link these loci were not successful.

Emotionality, exploratory behavior, and locomotion in aging inbred strains of mice.

Two inbred strains of mice, C57BL/6J and DBA/2J, ranging in age from 2 to 38 months, were tested in an open field using the free exploration method. Scores were obtained for locomotor activity, exploratory behavior and emotionality. Strain differences were observed for all three variables. Beginning at late maturity (12 months), locomotor activity decreased with increasing age. Exploratory behavior was at a low level for DBA/2J mice at all ages. For C57BL/6J mice, exploratory behavior decreased significantly between 2 and 6 months and remained stable thereafter. Emotionality remained unchanged with advancing age for both strains of mice.