A new rat congenic strain, WTC.ZI-zi, was produced after eleven generations of backcrossing between ZI strain as a donor strain and WTC strain as an inbred partner. WTC.ZI-zi/zi homozygous rats generally exhibit more conspicuous body tremor and much earlier occurrence of flaccid paresis than the original ZI strain. The average life span of the congenic strain is approximately nine months, which is also much shorter than that of the original ZI strain. Pathological analysis of the central nervous system of the congenic strain revealed more aggravated vacuolation and hypomyelination than in the original ZI strain. Establishment of the genetic profile with microsatellite markers showed that the congenic strain was genetically almost identical to the WTC strain except for a small chromosome segment bearing the zitter gene. Analysis of markers in this region implied that the length of the donor segment was approximately 13.4 centimorgans which corresponded to 0.65% of the total genome. Thus, these results suggested that expressional alterations of zitter gene were due to replacement of the genetic background from the original ZI strain to the WTC strain. Furthermore, the WTC.ZI-zi congenic strain could provide a refined tool for the analysis of zitter mutation, because the congenic strain has a strict control strain, WTC, and the length of the donor chromosome is genetically defined.
We recently constructed a comparative genetic map of the rat, mouse and human genomes based on information obtained from several databases. In this study, we performed chromosomal assignments of 29 rat genes with somatic cell hybrid clones, in order to clarify and extend the conserved regions in the rat and mouse genomes. As a result, the conserved regions were extended by 89 cM. Together with our previous report, the length of the conserved regions in the rat and mouse spans 847 cM on the mouse linkage map, indicating that 53% of the mouse genome is covered by homologous regions in the rat. In addition, four conserved regions were newly revealed. The method described in this study appears to be simple and efficient for constructing a whole genome comparative map of the rat and mouse.
The ontogenetic changes in responsiveness to benzodiazepine receptor ligands on ultrasonic vocalizations in rat pups from the age of day 3 to day 12 were evaluated. Rat pups, while separated from their dam and littermates and placed in a cold environment, emit ultrasonic vocalizations. These ultrasonic calls became attenuated dose-dependently in number and power after administration of the anxiolytic diazepam (0.25-1.0 mg/kg, sc), but the inhibitory effect of diazepam at the highest dose was less on day 6 and day 9. Moreover, type 1 benzodiazepine receptor ligands, Ro16-6028 and Ro23-0364 (0.5-2.0 mg/kg, sc), also dose-dependently attenuated the ultrasonic vocalizations 30-60 min after injection. The inhibitory effects of these drugs became more pronounced with the increasing age of the pup, and they were equivalent on day 12 to those in adult rats. These results suggest that different ontogenetic changes in development of two subtypes of central benzodiazepine receptors of pups might be related in the psychopharmacological mediation of the ultrasonic vocalization.
A cross-fostering experiment was conducted on two quite distinct subspecies of mice, domesticated laboratory mouse of CF#1 (Mus musculus domesticus) and Yonakuni wild mouse (Yk, Mus musculus molossinus yonakuni), to estimate the prenatal and postnatal maternal effects on body weight of offspring. Mating was done between subspecies, two or three females being mated to a male at nine-ten weeks of age. Two dams of different subspecies that littered at the same day were used as a group of foster dams. Litters were standardized to six young mice in order that a dam nursed three mice of her own litter and three mice from that of another subspecies dam. The litters were weaned at 3 weeks of age. The body weight of individual mice was determined at 1, 3, 6 and 10 weeks of age. The result demonstrated that prenatal maternal effects were more important than postnatal maternal effects in contributing to the variation in body weight at all ages examined. Prenatal maternal effects accounted for 61-96% and 35-92% of total variance in males and females, respectively; whereas postnatal effects accounted for 1-7% for males and 3-23% for females. Analysis for between postnatal within prenatal, and between prenatal within postnatal indicated that expression of the body weight of offspring was limited by the genetic type of their prenatal dam and influenced by the postnatal environment of nursing dam. The greatest body weight was attained by offspring born to prenatal CF#1 dams and nursed by postnatal CF#1 dams, followed by CF#1 offspring born to CF#1 dams and nursed by Yk dams, Yk offspring born to Yk dams and nursed by CF#1 dams and the lightest ones were Yk offspring born to Yk dams and nursed by Yk dams.
The mutation designated "open eyelids at birth" arose spontaneously in the BAN strain of the musk shrew (Suncus murinus). This is the first report on this kind of mutation in the shrew. Mating experiments suggested that the mutant character is controlled by an autosomal recessive gene with about 43% penetrance. The symbol oeb(open eyelids at birth) was proposed for the mutant gene. Affected shrews were fully viable and fertile. Phenotypically, the affected shrews were characterized by one or both eyelids open at birth. By 9 days of age, the exposed and dried eyeballs usually dropped off and became missing or sometimes looked microphthalmic. Except for the eye abnormality, the affected shrews showed no obvious external abnormalities. Light-microscopically, the affected shrews with missing eyes or microphthalmia-like eyes did not have complete eye structures, and only remnants of some eye tissue were observed. In the phenotypically normal oeb/oeb shrews with closed eyelids at birth, no histological eye abnormalities were noted. Thus, the mutant character observed may simply be caused by a failure of the eyelids to close.
We produced transgenic (Tg) gnotobiotic (GB) mice carrying human prototype c-Ha-ras genes and compared the incidence of colorectal tumors induced by 1,2-dimethylhydrazine (DMH) injection. At 7 to 11 weeks of age, germfree (GF) CB6F1-Tg Hras2 mice were inoculated with various mouse fecal suspensions or mixtures of bacteria isolated from mouse feces. Three weeks after bacterial inoculation, DMH was administered by subcutaneous injection at 20 mg per kg body weight for 20 weeks. Mice were euthanized 5 weeks after the last injection to investigate the number of colorectal tumors. The incidence of colorectal tumors was high in both Tg- and non-Tg-GF mice (100%). In Tg-specific pathogen-free (SPF) mice and Tg-GB-4 mice associated with basic mouse flora consisting of Escherichia coli, lactobacilli, Bacteroides and clostridia, the incidence of colorectal tumors was as high as that in GF mice. In Tg-SPF mice, the tumor score was higher than in Tg-GF mice (p<0.01), but no colorectal tumors were detected in non-Tg groups of SPF, and the tumor incidence was remarkably low in non-Tg-GB-4 mice. The tumor incidence and score in Tg- and non-Tg-GB mice varied depending on the bacterial combination in their intestine. These results indicate that the presence of human c-Ha-ras genes and intestinal bacteria substantially modify colorectal tumorigenesis induced by DMH.
In a series of experiment to elucidate the rule of amino acid requirements in the fowls from small to large ones, the fractional synthesis rates (FSR) of protein were determined to collect basal data on protein and amino acid metabolism in budgerigars as a small bird. Twenty young adult budgerigars were injected with 0.1 ml/10 g body weight containing 40 μCi/100 μmol phenylalanine/ml in a wing vein, and killed at 2 and 10 min after the injection. The FSR in the whole body, liver, proventriculs and gizzard, intestine and breast muscle were determined. The FSR were not the same in all tissues, and estimated values were highest in the liver (104.7), and followed by the intestines (68.0), whole body (55.2), proventriculs+Gizzard (46.8), heart (35.8) and breast muscle (26.9%/day).
A mouse feeder in common use in the US was modified to eliminate spillage, contamination by excreta and formation of food aggregates. The improved feeder consists of a glass jar which holds 100 g of meal-type feed, an inner metal mesh tube, a marble placed inside the inner mesh tube, and a snap-on metal lid. Female mice [B6C3F1 and CD-1(ICR)] were housed 5 animals/cage. Only slight contamination by feces, but not by urine, was observed in a 13-week feeding study with Japanese meal-type food and the improved feeder. Food spillage also decreased. Food consumption was significantly higher in cages with the conventional Japanese feeder than in the improved one, but no difference was observed between the two feeders in body weight gain.
Strain differences in erythrocyte glutathione (GSH) metabolism were studied in five inbred strains of Syrian hamster. Significant strain differences were found in the GSH level, rate of GSH regeneration, and the activity of hexokinase (HK). The rate of GSH regeneration did not correlate with the activity of HK. A gender difference was observed in the activity of HK. Our results indicate the possibility that Syrian hamster would be a model for studying the strain differences in the erythrocyte GSH metabolism.
In our laboratory, mice showing signs of osteoarthritic lesions with cinnamon colored (yellowish-brown) hair were discovered in a colony of B6C3F1 mice. This mouse is characterized by tiptoe walking and swelling and ankylotic changes in the ankle joint. As to radiographic findings, osteoarthritic changes, such as erosion and/or fusion of the bone tissue, were evident in the ankle joints. Histopathological characteristics included irregularity of articular surfaces caused by fissuring and/or erosion with degeneration of articular cartilage, as well as osteophytes with abnormal proliferation of chondrocytes in joint margin regions. Subsequently, ankylotic changes in the ankle joints were completed in the formation of a cartilaginous bridge and fusion of articular cavity with abnormal proliferation of cartilaginous or bone tissues. This mouse strain may provide an additional animal model that is valuable in the study of human osteoarthritis (OA).
In our laboratory animal facility, Sendai virus (HVJ) contamination occurred in a negative flow rack used for experimental infection with 4 strains of mouse-adapted influenza virus (Inf.V). Anti-HVJ antibody (Ab) was detected in 35/42 mice in the rack. To specify the strain of Inf.V contaminated with HVJ, experimental infection was performed by using A, B and D strains of Inf.V in each vinyl isolator. Anti-HVJ Ab was detected in all mice infected with A strain at day 28 post-infection. As a result of experimental infection with A strain of Inf.V which was treated with anti-HVJ mouse serum, the virus suspension was determined not to contain HVJ and allowed for experimental use in our facility. Since then, HVJ contamination has not occurred in our facility.