Donald J. Nash

EFFECTS OF X-IRRADIATION UPON POSTNATAL GROWTH IN THE MOUSE

1. The effect of x-irradiation of mouse embryos upon their postnatal development was measured by several responses: body weight changes from birth to maturity, lifetime fecundity, and total lifespan. The body weight responses are reported in this paper. Three genetically differentiated inbred strains of mice, Ba, K, and S, and all their possible hybrids, including reciprocals, were used. Pregnant females were exposed to single whole-body 250 pkv x-ray dosages from 20 r to 320 r on 64, 10½, 14½, and 17½ days gestation, as timed from the appearance of a vaginal plug. In addition the study included progeny irradiated on the day of birth without any irradiation of the maternal organism. Postnatal growth was followed from birth to 75 days of age, individuals having been weighed at birth, 12, 26, 40, 60 and 75 days.2. Body weights were adjusted by making use of the pooled regression coefficient of body weight on litter size over all treatments. Body weight response was found to be dependent on both level of irr...

CNS monoamine levels and motoric behaviors in the hotfoot ataxic mutant

Mice that were homozygous recessive for the single-gene mutation, hotfoot, showed profound and progressive motor disturbances in an open field after approximately the 4th postnatal week. Studies were undertaken to examine the role of the monoaminergic system in the behavioral and developmental expression of this neurological mutation. Relative to controls, 10-and 30-day-old hotfoot mice demonstrated a significantly attenuated response to the stimulating locomotor effects of amphetamine while adult hotfoot mice were motorically unaffected by amphetamine administration. 30-day-old and adult hotfoot mice also were hypothermic relative to phenotypically normal mice after amphetamine administration. Examination of monoamine levels and turnover revealed that hotfoot mice had significantly greater concentrations of norepinephrine associated with lower turnover in cerebellum and greater levels of serotonin in cerebellum and striatum, relative to phenotypic controls. In addition, mice born and raised by hotfoot dams demonstrated neurochemical alterations regardless of genotype. Both the neurochemical data and the developmental response to the general catecholamine agonist, amphetamine, suggest that the monaminergic neurotransmitter system may be altered as a consequence of the hotfoot mutation.

Ontogeny of Behavior in Mice Selected for Large Size

Development of 13 reflex responses and behavioral components of mice from the Goodale Giant inbred strain (G/Gw) was compared to that of a sample of 61 pups from a random-bred strain. Significant differences were observed between groups for several responses, but the direction of these differences was not consistent. Effects of rapid growth and increased size in G/Gw mice did not directly affect behavioral maturation.

EFFECTS OF X-IRRADIATION OF MICE EXPOSED IN UTERO DURING DIFFERENT STAGES OF EMBRYOLOGICAL DEVELOPMENT ON DURATION OF MATURE LIFE

1. Mature lifespans, 75 days of age to death, when the mice were exposed to irradiations at different stages of uterine development, showed reductions in mean longevity which were dependent on both x-ray dose and period of embryological cycle. The design for this study was factorial. There were five irradiation treatments, 0, 20, 80, 160 and 320 r, six embryological stages: untreated, 6½, 10½, 14½, 17½ and newborn (19½) days of uterine development, two sexes and nine mouse strains. Three of the inheritance groups were inbred strains and six were the reciprocal crosses of these strains. Efforts were made to obtain two mice for each cell of the design. However, some treatments were so severe that this was impossible. X-ray dosages of 160 and 320 r at embryological ages 6½, 10½ and 14½ days were too lethal to obtain the requisite number of progeny in these groups.2. Six hundred and forty-seven completed mouse lives were collected. Mature lifespan ranged downward from 1194 days for the males and 921 days for ...

Morphological and physiological changes in mice (Mus musculus) selected for large size

Abstract 1. 1. Organ weight studies were carried out on young and aged mice of the Goodale Giant Strain (G/Gw). 2. 2. G/Gw mice have increased body weight (over 40 g), but are normally proportioned without any evidence of obesity. 3. 3. Most organ weights of the G/Gw increased in direct proportion to the increase in body weight although the pituitary, liver and kidneys exhibited relatively larger sizes than in normal sized studies. 4. 4. The increase in liver weight was found to be associated with an increased level of liver glycogen.

Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR Mice

1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fishers protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA receptor antagonists, a finding which may be important given the NMDA receptor hypofunction hypothesis for the etiology of schizophrenic symptoms.

Hyperglycemia in mice of the Goodale Giant (G/GW) strain

Abstract Mice of the Goodale Giant strain have a 60-day weight which is over twice that of normal mice and have a non-fasting glucose level of 250 mg/dl. Body composition and insulin levels are normal; however, growth hormone levels are elevated and glucose tolerance is abnormal. The mild hyperglycemia is associated with the rapid rate of growth and elevated level of growth hormone.

Histochemical studies of wound healing in the hair-loss mouse

SummaryAdult female hair-loss (hl) mice (Mus musculus) were given incised wounds through the full thickness of the dorsal skin. At specified intervals there after (i. e., 1, 2, 4, 6, 12, and 20 hours), the animals were sacrificed and the wound sites were excised, processed, and sectioned. Enzyme and carbohydrate histochemical procedures were carried out on frozen and paraffin sections respectively. Nonspecific esterase was demonstrated in one hour wounds and a slight increase was observed through six hours. No other enzyme histochemical procedure gave a satisfactory reaction in the wound site. The Periodic Acid-Schiff reaction for carbohydrates revealed a steadily increasing reaction from one to six hours and a decrease in intensity by twelve hours. The causative agent for the PAS reaction may be serum glycoproteins transported to the wound site as part of the inflammatory process.ZusammenfassungErwachsenen weiblichen Mäusen (Mus musculus) wurde die dorsale Haut durchgeschnitten. Nach gegebenen Zeiten (1, 2, 4, 6, 12 und 20 Stunden) wurden die Tiere getötet und die Wunden exzidiert, vorbereitet und ge schnitten. Die Fermenthistochemie wurde an Gefrierschnitten durchgeführt, während die Histochemie der Kohlehydrate an Paraffinschnitte ausgeführt wurde. Die Esterase konnte bei einem Wundalter von einer Stunde dargestellt werden; sie war ein bißchen stärker in 6 Stunden alten Wunden. Keine andere Ferment histochemie, die an den Präparaten durchgeführt wurde, ergab befriedigende Resultate. Die sogenannte “Periodic acid-Schiff”-Reaktion für Kohlehydrate zeigte eine regelhafte Verstärkung in den 1 bis 6 Stunden alten Wunden; dann nahm die Intensität in den 12 Stunden alten Wunden ab. Die „PAS”-Reaktion könnte dadurch entstanden sein, daß die Serum-glycoproteine durch Entzündungs prozesse in die Wunden gelangten.

Interaction of neonatal irradiation and single-genes upon growth and behavior in mice

Abstract Postnatal growth and behavior following neonatal irradiation were studied in congenic strains of mice. Mice were genetically similar except for single-gene substitutions at either the steel or dominant spotting loci. Adult behavior was measured by locomotion and elimination in the open field and by spontaneous activity in exercise wheels. In general, neonatal irradiation caused a decrease in body weight, activity in exercise wheels, and elimination in the open field, but an increase in locomotion in the open field. Significant differences due to genotype and sex were observed for locomotion and body weight. Differential responses of the genotypes to neonatal irradiation were observed in body weight and in activity in exercise wheels. The genotypes, in order of increasing sensitivity, were +/+, W a /+, and Sl gb /+.

Effects of prenatal x-irradiation on development and postnatal viability of inbred and hybrid mice.

Studies of the effects of prenatal x-irradiation of mammals have emphasized in recent years long-term pathological and functional investigations. These inves tigations have included studies on growth ( Murphree and Pace, 1960 ; Nash and Gowen, 1962 ; Parish, Murphree and Hupp, 1962 ; Rugh, Duhamel, Chandler and Varma, 1964), reproduction (Russell, Badgett and Saylors, 1960 ; Rugh and Jack son, 1958 ; Nash, 1969) , and postnatal mortality and hifespans ( Nash and Gowen, 1965 ; Rugh and Wohlfromm, 1965 ; Sikov, Resta and Lofstrom, 1969). In spite of the obvious significance to human populations, relatively little work has been done to explore the influence of genetic background in conditioning the response of embryos to x-irradiation. Most of the earlier studies either have utilized animals of unknown heterogeneous origin or single strains of uniform origin. A few studies have demonstrated the significance of genetic variability in embryonic response (Rugh, 1958; Callas, 1962; Nash and Gowen, 1962, 1965; Dagg, 1963; Nash, 1969). The recent review of Brill, Nance, Engel, Glasser, and Forgotson (1967) has pointed out the basic similarities between laboratory animal studies and long-term, postnatal effects observed in humans that have been exposed to prenatal irradia tion. The studies reported in the present paper were designed to examine effects of prenatal x-irradiation upon the responses of inbred and hybrid mouse embryos as measured by morphological changes and changes in postnatal viability. The mice that were used in these studies were obtained from first pregnancies of matings within and among three inbred strains: BALB/Gw, K/Gw and S/Gw. Descriptions of the characteristics of the strains are provided in previous papers (Nash and Gowen, 1962, 1965). The matings produced progeny which were either inbred or hybrid, and provided nine different inheritance types. Mated females were examined daily for the presence or absence of a vaginal plug, the plug being the sole criterion used to time the period of gestation and the approximate age of embryos at irradiation. The afternoon of the day on which the plug was observed was considered to be day @ of gestation. Females were irradiated at 4 PM, and the gestational ages of the embryos at the time of treatment were considered to be approximately 6@, 1O@,14@or 17@days. Developmentally, these ages correspond to a time shortly after implantation, a period of major organogenesis, a period of minor organogenesis, and a time of rapid fetal growth, respectively. However, there are a number of factors which 1 This work has received assistance from Contract AT (11-1)—107 from the Atomic En ergy Commission and U. S. PublicHealth ServiceGrant HD—01898from the NationalInsti