Sleep-time variation for ethanol and the hypnotic drugs tribromoethanol, urethane, pentobarbital, and propofol within outbred ICR mice.

To evaluate the phenotypic variation within a commercial outbred mouse stock, we examined sleep-time (or duration of loss of righting reflex) of outbred ICR mice after i.p. injection of ethanol (4.0 g/kg of body weight), urethane (1.3 g), tribromoethanol (250 mg), and pentobarbital (60 mg), and after i.v. injection of propofol (30 mg). We observed high-grade individual differences in sleep-time that ranged from 0 to 179 min, 83.1 +/- 4.3 (mean and SEM of 100 mice) for ethanol; 0 to 169 min, 64.5 +/- 3.1 for pentobarbital; 0 to 160 min, 36.6 +/- 3.6 for urethane; 0 to 120 min, 21.5 +/- 2.2 for tribromoethanol; and 3 to 20.5 min, 7.1 +/- 0.3 for propofol. This extensive phenotypic variance within the outbred stock was as great as the variation reported among inbred strains or selected lines, and the varied susceptibility within the colony was inherited by Jcl:ICR-derived inbred strains IAI, ICT, IPI, and IQI. The range of sleep-time variance for ethanol, pentobarbital, urethane, tribromoethanol, and propofol within four-way cross hybrid Jcl:MCH(ICR) mice was 86.6%, 63.3%, 124%, 61.0%, and 53.1% that of outbred Jcl:ICR mice, respectively. The present study indicates that phenotypic variance within an outbred Jcl:ICR stock was at high risk for susceptibility to the drugs that depress the central nervous system and that Jcl:ICR-derived inbreds may be an excellent source of animal models for studying the anesthesia gene.     

Investigation of the histocompatibility of the NYA:NYLAR mouse colony by skin grafting.

The histocompatibility status of the Nya:NYLAR mouse colony was studied by exchange of skin grafts between female mice. The colony had been divided into two portions since 1962, a larger, outbred stock (Nya:NYLAR), and a smaller, inbred strain (NYLR/Nya). The results of skin graft exchanges between mice of the inbred strain indicated that they were skin-compatible. There was weak skin-incompatibility within the outbred stock and between this stock and the inbred strain, and strong skin-incompatibility between the outbred stock and outbred Webster Swiss mice.     

Polymorphism of esterase 11 in Mus musculus,a further esterase locus on chromosome 8

A further esterase, esterase 11, which exhibits a polymorphism detectable by electrophoresis, has been observed in the house mouse, Mus musculus. In 15 inbred strains and two outbred strains, the ES-11A phenotype has been found, composed of two bands of enzyme activity of greater anodal electrophoretic mobility than the two bands of the ES-11B phenotype found in one inbred strain, one wild stock, and 101 wild mice. In F₁ hybrids (IS/Cam×C57 BL/Gr), the phenotype shown corresponds to a mixture of the two parental phenotypes. In backcrosses, ES-11 segregates as an autosomal gene, designated Es-11, closely linked to Es-2 and Es-5 on chromosome 8.This work was supported by the Medical Research Council.     

Rates of micronuclei induction in different mouse strains

It has previously been shown that the inbred mouse strain MS/Ae was more sensitive in the micronucleus test to several mutagenic agents than outbred mice. To elucidate the possible influence of inbreeding, several inbred strains including MS/Ae, AKR, BALB/c, C57 BR were compared to the two OF1 and NMRI outbred strains. The 3 mutagenic agents MNNG, MMC and MMS all induced a significantly higher number of micronuclei in the MS/Ae strain than in any of the other mouse strains. AKR was especially resistant to the alkylating agents MMS and MNNG. Hence, except for the MS/Ae mouse strain, no inbred strain showed a systematically higher sensitivity than the outbred strains for all of the 3 mutagenic agents used.     

Inbred and outbred mice have equivalent variability in a cockroach allergen-induced model of asthma

Outbred mice traditionally are considered to display high variability, thereby limiting their use in some studies. Researchers frequently are encouraged to use inbred strains of mice because of the greater homogeneity of these experimental animals. We compared the pulmonary inflammatory response of inbred BALB/cJ mice to that of outbred HSD-ICR mice by measuring multiple variables, including cytokines, chemokines, number of pulmonary inflammatory cells, and respiratory parameters. Cockroach allergens induced significant pulmonary inflammation in both BALB and ICR mice. Our comparisons of the coefficients of variance for 148 discrete data sets for each strain or stock indicated that BALB and ICR mice have roughly equivalent intrastrain or -stock variability in our model of asthma-like pulmonary inflammation. The average coefficient of variance, calculated as the ratio of the SD to the mean of a data set, was 0.35 ± 0.34 for BALB mice compared with 0.31 ± 0.32 for ICR mice. In conclusion, inbred BALB and outbred ICR mice have roughly equivalent intrastrain or -stock variability in a murine model of asthma-like pulmonary inflammation.     

NIH/Ola: a highly productive inbred strain of laboratory mouse

According to historical records the NIH/Ola strain was developed from outbred 'Swiss' mice imported into the USA by Dr C. Lynch in 1926. A comparison of biochemical markers in strain NIH/Ola and other strains such as SJL and SWR derived from the same foundation stock supports the historical records. Data on litter size, length of gestation, bodyweight to 70 days of age, and reproductive performance when housed in polygamous groups of up to 10 females per male were compared with similar data on inbred CBA/CaOla and C57BL/10ScSnOla mice. NIH/Ola inbred mice had an exceptional reproductive performance, producing about 1.8 young weaned/female/week when housed as monogamous pairs over a period of 20 weeks, compared with less than 1.0 young/female/week with the other 2 strains. NIH/Ola mice were also extremely tolerant to mating in polygamous groups of up to about 8 females per male. Mating ratios of over 2-3 females per male resulted in a marked decline in the total number of litters produced per female in C57BL/10ScSnOla and CBA/CaOla, but this reduction was not nearly so marked in NIH/Ola. It is concluded that the NIH/Ola inbred strain may be particularly useful in studies such as teratology where a high reproductive performance needs to be combined with the advantages of a fully inbred strain.     

Blood pressure in 15 inbred mouse strains and its lack of relation with obesity and insulin resistance in the progeny of an NZO/HILtJ × C3H/HeJ intercross

We characterized the systolic and diastolic blood pressures of 10-week-old males from 15 inbred mouse strains and found that blood pressures among strains were continuously distributed and that strain C3H/HeJ had the lowest mean systolic and diastolic pressure (100.5 ± 3.2 and 66.8 ± 3.5 mmHg), and a strain with obesity and diabetes, NZO/HILtJ, had the highest (132.4 ± 3.1 and 86.6 ± 6.9 mmHg). To understand the relationship of blood pressure with insulin resistance and obesity, we produced F₁ and F₂ progeny from reciprocal crosses of NZO, the strain with obesity, diabetes, and high blood pressure, and the strain with the lowest blood pressures, C3H/HeJ. Mean systolic pressures of 10-week-old (NZO × C3H)F₁ and (C3H × NZO)F₁ males were similar to each other (114.9 ± 3.8 and 117.2 ± 5.0 mmHg) and were intermediate to those of the parental strains. Systolic pressure of F₂ males (n = 223) was distributed normally about the mean, suggesting that blood pressure is a polygenic trait. The body mass index (BMI) and plasma insulin levels of F₂ progeny correlated significantly and positively with plasma leptin levels, suggesting that obesity is associated with insulin resistance. In contrast, systolic pressure did not correlate with BMI, plasma leptin levels, and plasma insulin levels, suggesting that genes underlying the development of hypertension in this intercross are not associated with the development of obesity and insulin resistance. Our results demonstrate that the progeny of NZO and C3H intercrosses are a practical and powerful tool for identifying blood pressure genes and for understanding human polygenic hypertension.(Fumihiro Sugiyama) These authors contributed equally to this study.     

Influences of inbreeding and genetics on telomere length in mice

We measured telomere lengths of blood leukocytes in several inbred and outbred mammalian species, using a telomere-specific fluorescent probe and flow cytometry. Humans, non-human primates, and three outbred populations of Peromyscus mice (Peromyscus leucopus, Peromyscus maniculatus, and Peromyscus polionotus) have short telomeres. Two common strains of laboratory mice, C57BL/6J and DBA/2J, have telomeres several times longer than most other mammals surveyed. Moreover, the two inbred laboratory mouse strains display significantly different telomere lengths, suggesting the existence of strain-specific genetic determinants. To further examine the effects of inbreeding, we studied three Peromyscus leucopus inbred lines (GS109, GS16A1, and GS16B), all derived from the outbred P. leucopus stock. Telomeres of all three inbred lines are significantly lengthened relative to outbred P. leucopus, and the three lines display strain-specific significantly different telomere lengths, much like the C57BL/6J and DBA/2J strains of M. musculus. To further characterize the genetic inheritance of telomere length, we carried out several crosses to obtain hybrid F₁ mice between parental strains displaying the phenotype of long and short telomeres. In all F₁ mice assayed, peripheral blood leukocyte telomere length was intermediate to that of the parents. Additionally, we generated F₂ mice from a cross of the (P. leucopus outbred × GS16B)F₁. Based on the distribution of telomere length in the F₂ population, we determined that more than five loci contribute to telomere length regulation in Peromyscus. We concluded that inbreeding, through unknown mechanisms, results in the elongation of telomeres, and that telomere length for a given species and/or sub-strain is genetically determined by multiple segregating loci.     

Enzyme polymorphism in feral, outbred and inbred rats (Rattus norvegicus).

Polymorphism at 25 loci coding for liver enzymes was studied in two feral, three outbred and three inbred rat strains by starch gel electrophoresis. No variation was found at 14 loci, and a low degree of polymorphism was detected at three. Eight loci were polymorphic in more than one population. The average degree of heterozygosity per locus per individual feral rat was 0-07. The degrees of heterozygosity observed in the outbred and inbred strains were lower, from 0-006 to 0-012. Contrary to expectation, the inbred strains were neither monomorphic nor appreciably less heterozygous than the outbred ones. The heterozygosity of the inbred strains was primarily due to two polymorphic loci, G-3-pdh and alpha-Gpdh. The reason for this polymorphism is probably the superior homeostasis of the heterozygotes.     

Strain differences in guinea pigs' bronchial sensitivity to acetylcholine

The bronchial sensitivity to acetylcholine (ACh) of guinea pigs of various strains was investigated to clarify strain differences. Inbred Strain 2, Strain 13 and JY-1 and non-inbred Hartley strain (two colonies) were used in this experiment. (1) Guinea pigs were exposed to 0.08% ACh aerosol and the time needed to produce falling down (TNPFD) was determined. Mean +/- standard error of TNPFD (n = 14 per group) of animals was 182 +/- 28 sec, 148 +/- 22 sec, 210 +/- 30 sec, 342 +/- 24 sec and 406 +/- 36 sec in Strain 2, Strain 13, JY-1, Hartley (Japan SLC) and Hartley (Hitachi), respectively. There was a significant difference in TNPFD between inbred strains and non-inbred strains (P less than 0.05 or P less than 0.01), indicating that inbred strains had higher sensitivity. (2) Guinea pigs were exposed to 20-5000 micrograms/ml ACh for 2 min. The mean dose threshold as determined by transcutaneous oxygen pressure was 524 micrograms/ml, 424 micrograms/ml, 614 micrograms/ml, 1317 micrograms/ml and 1651 micrograms/ml (n = 14 per group) in Strain 2, Strain 13, JY-1, Hartley (Japan SLC) and Hartley (Hitachi), respectively. Inbred strains showed lower dose thresholds than non-inbred strains. (3) Isolated trachea-lungs of 5 guinea pigs were perfused with 10(-9)-10(-5) g/ml ACh to determine strain differences. Dose response curves of animals of inbred strains shifted to the left (lower concentrations), unlike those of non-inbred strains, suggesting that inbred strains had higher sensitivity to ACh than non-inbred strains.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in survival among germfree mice following transfer to a conventional colony.

Sex and strain differences in survival were studied in 7-9 month old germfree mice following transfer to a conventional colony. One outbred and three inbred strains were observed. All outbred CD-1 mice survived transfer and in 4 months increased their weight by 50%. The majority of inbred mice survived 7 months after transfer. Sex differences in survival were evident throughout the experimental period and were most marked 7 months after transfer. An unexpected new finding was the viability of the male sex in germfree mice after transfer. Possible explanations are considered.     

Restriction fragment length polymorphism of cardiac myosin heavy chain gene in rats and its strain distribution

The distribution of an RFLP in EcoRI fragments of the cardiac myosin heavy chain gene among 29 strains of laboratory rats was examined. Southern blot hybridization of rat genomic DNAs with rat cardiac myosin heavy chain cDNA as a probe demonstrated an interstrain variation in one of eight EcoRI fragments. Of the 28 inbred strains examined, 10 had a fragment of 10 kbp, whereas 18 had a fragment of 7.5 kbp. The 15 samples of the remaining strain (Iar: WI outbred stock) had fragments of either 7.5 kbp or 10 and 7.5 kbp, indicating that this strain has maintained heterogeneity of these fragments.     

Differential inbreeding tolerance in two geographically distinct strains of root voles Microtus oeconomus

Two geographically distinct strains of Microtus oeconomus, each consisting of an inbred (sibling mating) and an outbred treatment group, were bred in the laboratory over three generations to determine the effects of inbreeding on reproductive parameters, growth rates of young and paternal behavior The southern strain (orginating from southern Norway) suffered from depressed reproductive rate (litter size and pregnancy rates) most likely due to inbreeding, while no effects of inbreeding were detected m the northern strain (originating from northern Norway) This result questions previous generalizations about inbreeding tolerance at the species level for Microtus Growth rates and paternal behavior did not differ significantly between inbred and outbred voles in either strain Inbreeding depression rather than inbreeding avoidance is the most likely mechanism behind the depression in reproductive parameters of inbred southern voles This is suggested by the decrease in the proportion of breeding pairs with the number of generations of inbreeding, and by the reduced litter size of inbred compared with outbred pairs Field and laboratory studies have shown that behavioral and demographic traits, possibly related to the degree of inbreeding, differ between the two strains which suggests that inbreeding tolerance might be a life history adaptation     

Leishmania major: culture media, mouse strains, and promastigote virulence and infectivity

Promastigotes of Leishmania major were isolated from an infected mouse in two media, blood agar and Schneider's medium + 30% fetal calf serum, and maintained continuously for over 1 year. Infectivity studies in two strains of mice, outbred CD1 strain and inbred BALB/c strain, showed that promastigotes grown in Schneider's medium maintained infectivity to BALB/c mice throughout the period of cultivation. Infectivity to CD1 strain mice was progressively lost. Promastigotes grown in blood agar medium, however, lost infectivity to both strains of mice at a faster rate than promastigotes grown in Schneider's medium.     

Ventilatory phenotypes among four strains of adult rats.

Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive (n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O(2)-88% N(2)), hypercapnia (7% CO(2)), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO(2) (P < 0.001), an accentuated ventilatory response to exercise (P < 0.05), and an accentuated ventilatory roll-off during hypoxia (P < 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains (P > 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO(2) sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO(2) sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms.     

Evidence for general cognitive ability (g) in heterogeneous stock mice and an analysis of potential confounds

The heterogeneous stock (HS) is a genetically outbred line of mice established more than 30 years ago from an 8-way cross of C57BL/6, BALB/c, RIII, AKR, DBA/2, I, A/J and C3H inbred mouse strains. The present study compared the performance of 40 HS mice across a battery of diverse cognitive tasks under a variety of motivations. Indices of emotionality were also included in order to assess their influence on performance. All measures of ability loaded positively on an unrotated first principal component that accounted for 31% of the variance, suggesting the presence of a common factor of general cognitive ability ( g ) underlying all tasks. A first factor derived from anxiety indices correlated nonsignificantly with all cognitive tasks and nonsignificantly with this g factor, supporting the hypothesis that the factor is cognitive rather than temperamental in nature. The factor was also robust in relation to outliers and sex differences, accounting for 28% of the variance after removal of outlier individuals and also after correcting for variance owing to sex differences. A general cognitive ability ( g ) appears to underlie the performance of HS mice on a battery tapping diverse cognitive demands.     

A new inbred Wistar-Kyoto rat substrain exhibiting apparent salt sensitivity and borderline hypertension

The normotensive Wistar-Kyoto (WKY) rat strain is a traditional control for the spontaneously hypertensive rat (SHR). We found trait differences between two inbred normotensive WKY strains, derived originally from different vendors, and compared these two strains from La Jolla-Taconic Farms (WKY/lj-tf) and La Jolla-Charles River (WKY/lj-cr) with the inbred SHR/lj-cr for cardiovascular, diurnal, and activity traits under normal and high (8%) NaCl diets. Marked genetic diversity was found between the two vendor-derived WKY. By using an extended study design and radiotelemetry, we compared WKY/lj-cr, WKY/lj-tf, and SHR/lj-cr with the following results: systolic pressure (120 +/- 1, 133 +/- 1, 168 +/- 3 mmHg, respectively); diurnal variation in heart rate (DeltaHR: 46 +/- 3, 71 +/- 4, 57 +/- 2 beats/min, respectively); and salt sensitivity of arterial pressure (Deltasystolic: 10 +/- 1, 21 +/- 1, 20 +/- 1 mmHg, respectively). The WKY/lj-tf genotype apparently results in compromised control of arterial pressure and heart rate, especially during high NaCl intake, and greater susceptibility to high pressure (i.e., high NaCl-induced secondary changes). WKY/lj-tf thus constitutes a new inbred borderline hypertensive WKY substrain offering unique opportunities for genomic studies into the development of genetic hypertension.     

Characterization of temperature-sensitive strains of Neospora caninum in mice

Temperature-sensitive (ts) strains of the Neospora caninum tachyzoites were selected by chemical mutagenesis and selection for growth at 32 C. Three ts strains and the parental, N. caninum wild-type strain, NC-1, were examined in the present study for their ability to cause disease in inbred BALB/c mice, outbred ICR mice, and chemically immunosuppressed ICR mice. In BALB/c mice, all 3 strains failed to induce clinical disease, whereas infection with the NC-1 strain caused central nervous system disease and death in some mice. No disease was observed in ICR mice inoculated with the 3 ts strains or the NC-1 strain. All immunosuppressed ICR mice inoculated with the NC-1 strain died, whereas no immunosuppressed mice inoculated with the NCts-4 strain and only 1 of 5 mice inoculated with the NCts-8 and NCts-12 strains died. The NCts-4 and NCts-12 strains reverted to a wild-type phenotype when grown at 37 C. Vaccination of BALB/c mice with live, but not frozen NCts-8 strain tachyzoites induced significant (P < 0.05) protection following NC-1 strain challenge.     

Ultrasonic measurement of scleral cross-sectional strains during elevations of intraocular pressure: method validation and initial results in posterior porcine sclera

Background. Scleral biomechanical properties may be important in the pathogenesis and progression of glaucoma. The goal of this study is to develop and validate an ultrasound method for measuring cross-sectional distributive strains in the sclera during elevations of intraocular pressure (IOP). Method of Approach. Porcine globes (n?=?5) were tested within 24 hs postmortem. The posterior scleral shells were dissected and mounted onto a custom-built pressurization chamber. A high-frequency (55-MHz) ultrasound system (Vevo660, VisualSonics Inc., Toronto) was employed to acquire the radio frequency data during scans of the posterior pole along both circumferential and meridian directions. The IOP was gradually increased from 5 to 45?mmHg. The displacement fields were obtained from correlation-based ultrasound speckle tracking. A least-square strain estimator was used to calculate the strains in both axial and lateral directions. Experimental validation was performed by comparing tissue displacements calculated from ultrasound speckle tracking with those induced by an actuator. Theoretical analysis and simulation experiments were performed to optimize the ultrasound speckle tracking method and evaluate the accuracy and signal-to-noise ratio (SNR) in strain estimation. Results. Porcine sclera exhibited significantly larger axial strains (e.g., -5.1?±?1.5% at 45?mmHg, meridian direction) than lateral strains (e.g., 2.2?±?0.7% at 45?mmHg, meridian direction) during IOP elevations (P's?相似文献   

Relationship between frequencies of univalents and meiotic segregation in different mouse strains and their hybrids

Although univalents in diakinesis are often used as an estimator for chromosome mis-segregation during meiosis, no clear-cut relationship was demonstrated between both phenomena. In this study, the frequencies of autosomal and gonosomal univalents in diakinesis were related to the frequencies of aneuploid metaphase-II gonocytes during spermatogenesis and oogenesis of different mouse strains and their hybrids (inbred strains: DBA/2J, C₅₇Bl; outbred strain; Swiss, inbred x outbred hybrids: Swiss × C₅₇Bl, C₅₇Bl × Swiss, inbred x inbred hybrids: DBA/2J × C₅₇Bl, C₅₇Bl × DBA/2J). As far as the frequencies of univalents are concerned, they were shown to be strain-dependent and similar in both sexes. Moreover, there is a high non-disjunction rate of DBA males and PMSG-HCG-primed DBA females. Aneuploidy in metaphase II is also strain-dependent but different in both sexes; in the male, a clear decrease of aneuploidy frequencies is observed as compared to the frequency of univalents. This decrease does not occur in females.