A few characteristics of mouse having high sensibility to anaphylatic shock separated from El mouse (author's transl)]

During an experiment of shaking in El mice, a strain which was less susceptible to convulsion was found out. In this strain (ASK), the mortality to anaphylactic shock and susceptibility to audiogenic seizure were compared with five other strains of mice. Six strains of mice (ASK, EL, IDT, JCC-ICR, dd, C57BL/6J) were sensitized by two subcutaneous injections with 2 mg/head of crystalline egg albumin at five and six weeks of age, and then challenged by the intravenous injection of 0.125, 1, 8, 64, 512 and 4096 mug/head at seven weeks of age. In both sexes of ASK strain, the mortality was the maximum (75--95%) after the challenge of 8--4096 mug egg albumin. The mortality of the female El and IDT and the both sexes of JCL-ICR strains was middle (55--70%) after the challenge with 64 mug egg albumin, while that of other strains (dd and C57BL/6J) was very low (0--20%). The susceptibility of 3-weeks-old mice of ASK, El, IDT, JCL-ICR and dd strains was low (1.9--19.0%), whereas mice of DBA/2 strain showed a very high susceptibility (80%) to 110 phons.     

Cytochemical correlates of structural sexual dimorphism in glandular tissues of the mouse. I. Studies of the renal glomerular capsule.

The parietal epithelium of Bowman's capsule has been analyzed by enzyme cytochemistry in kidneys of mice (C57BL/6J) from birth to 50 days of age. There is a greater tendency for cells in the central portions of the capsular crescent to be cuboidal in post-pubertal males than in pre-pubertal mice of either sex or in post-pubertal females where they are generally squamous; moreover, these heightened capsular cells have a distinct microvillous border. Cytochemical procedures were selected which might confirm the morphological suggestion that the cuboidal parietal epithelium possesses an absorptive capacity. The oxidoreductase activity of the mitochondria of the cuboidal cells of this layer is comparable to that of the columnar cells of the proximal convoluted tubule. The cytochrome oxidase activity of the mitochondria in both of these segments of the nephron is intense. This is in sharp contrast to the unreactive mitochondria in the squamous cells of the parietal epithelium. Furthermore, a striking heterogeneity in the degree of cytochrome oxidase activity is evident in the mitochondria of the cuboidal parietal cells as well as in the cells of the proximal tubules. In the former cells, active mitochondria were generally found near microvilli at the apical ends and in the areas of the basal infoldings whereas those in a central position were more frequently unreactive. The brush border of the cuboidal capsular epithelium had prominent alkaline phosphatase and aminopeptidase activities as has previously been observed in other brush borders. Functional capacity corresponding to the morphological and cytochemical specialization of the cuboidal capsular cells was demonstrated by their uptake of horseradish peroxidase. This exogenous protein tracer could be seen in apical vacuoles and phagosomes in the cuboidal parietal epithelium. The cytochemical resemblance of the cells of this epithelium to those of the proximal convoluted tubules suggests a similar involvement in resorption and perhaps in active transport. A possible relationship of this differentiation of the capsular epithelium to the proteinuria normal for adult male mice is discussed.     

Requirement for leptin in the induction and progression of autoimmune encephalomyelitis

Recent evidence indicates that leptin modifies T cell immunity, and may provide a key link between nutritional deficiency and immune dysfunction. To study the influence of leptin on autoimmunity, susceptibility to experimental autoimmune encephalomyelitis induced by immunization with a myelin-derived peptide was examined in leptin-deficient, C57BL/6J-ob/ob mice, with or without leptin replacement, and in wild-type controls. Leptin replacement converted disease resistance to susceptibility in the C57BL/6J-ob/ob mice; this was accompanied by a switch from a Th2 to Th1 pattern of cytokine release and consequent reversal of Ig subclass production. Our findings suggest that leptin is required for the induction and maintenance of an effective proinflammatory immune response in the CNS.     

Adrenal function and the effect of a high-fat diet on C57BL/6J and C57BL/6J-ob/ob mice.

In C57BL/6J mice and the ob/+ and ob/ob mutants total plasma corticosterone levels were found to be statistically different. In C57BL/6J mice the level was 1.9 +/- 0.2 mug/100 ml plasma, in ob/+ mice 8.6 +/- 1.6 mug/100 ml and in ob/ob mice 13.7 +/- 1.5 mug/100 ml. The percentage of protein-bound corticosterone as well as the free endogenous corticosterone levels were also different. Feeding a high-fat diet to young C57BL/6J and C57BL/6J-ob/ob mice for a period of 4 weeks had no effect upon blood glucose, plasma insulin and plasma corticosterone levels. The significantly higher increase in body weight of the high-fat diet groups of both lines of mice was mainly due to fat cell hypertrophy.     

Gender influences infectivity in C57BL/6 mice exposed to mouse minute virus

Two natural outbreaks of mouse minute virus (MMV) are described. Observations during management of the naturally infected colonies led to a study in which 4-wk-old C57BL/6NCr and C57BL/6Tac mice were inoculated oronasally with an immunosuppressive variant of MMV (MMVi), as were adult C57BL/6NCr lactating dams or their pups (age, 10 d). By day 28 postinoculation, 100% of the 4-wk-old male C57BL/6NCr and C57BL/6Tac mice, 56.2% of 4-wk-old C57BL/6NCr female and 62.5% of 4-wk-old C57BL/6Tac female mice, 100% of adult lactating C57BL/6NCr dams, and 100% of inoculated pups (10 d) had seroconverted. Serologically positive nursing dams did not infect their nursing pups. In contrast, when nursing pups were inoculated, 100% of their dams seroconverted by 28 d postinoculation. Only 1 of 4 facility sentinels (Tac:SW female mice) seroconverted to MMVi and none of the 4 research sentinels (Tac:SW female mice) seroconverted under a once-weekly bedding transfer program. Consequently, 4 new research Tac:SW sentinels of each gender (n = 8) were placed in known-positive cages at cage-change; 100% of the male mice but 0% of the females seroconverted by day 48. Study results suggest gender influences both infectivity and the ability to detect subclinical infections of MMVi. Other factors that may influence detection of MMV include mouse strain or stock, short shedding period, and prolonged time between cage changes. In light of the data from both the natural infections and the experimental cases, cessation of breeding likely will be beneficial when trying to eradicate this virus.     

Role of phosphatidylinositol-3-kinase-gamma (PI3Kgamma)-mediated pathway in 17beta-estradiol-induced killing of L. mexicana in macrophages from C57BL/6 mice

We recently demonstrated that 17beta-estradiol (E2) enhances killing of Leishmania mexicana in macrophages from both male and female DBA/2 mouse by increasing nitric oxide (NO) production. Here, we analyzed the effect of E2 on leishmanicidal activity and cytokine production by bone marrow-derived macrophages (BMDMs) from male and female C57BL/6 mice in vitro, specifically examining the role of phosphatidylinositol-3-kinase-gamma (PI3Kgamma) in E2-induced parasite killing. Unlike its effect on macrophages from both male and female DBA/2 mice, E2 only increased leishmanicidal activity in macrophages from female C57BL/6 mice, which was evident by a significant reduction in both infection rates and infection levels compared to sham controls. E2-treated BMDMs from female C57BL/6 mice expressed higher levels of interferon-gammaRalpha, and also produced more interleukin (IL)-12, IL-6 and NO than both the sham controls and E2-treated male-derived macrophages. Sham-treated BMDMs from female PI3Kgamma-/- C57BL/6 mice displayed lower infection rates and infection levels compared to sham-treated wild-type (WT) macrophages. However E2, unlike its effect on macrophages from female WT C57BL/6 mice, failed to reduce infection rates and infection levels in BMDMs from female PI3Kgamma-/- mice. Interestingly, E2-treated BMDMs from female C57BL/6 mice produced significant amounts of inflammatory cytokines and NO in levels comparable to those observed in sham-treated PI3Kgamma-deficient macrophages as well as E2-treated macrophages from WT mice. These findings show that E2 exerts a distinct effect on leishmanicidal activity of macrophages from male versus female C57BL/6 mice. In addition, they suggest that PI3Kgamma is not required for E2-induced cytokine and NO production in L. mexicana-infected macrophages from female C57BL/6 mice but it may be involved in parasite clearance from these cells.     

Pancreatic lesions of small-obese mice (C57BL/6 J-ob/ob) with hyperglucagonemia

Male Small-obese mice (Small-ob) which derived from a C57BL/6 J-ob/ob mouse colony were examined histopathologically at 13-, 39-, and over 52-week-old. C57BL/6 J-ob mice (?/+: Non-ob, ob/ob: Ob) were studied as controls. In Small-ob mice, plasma glucagon concentration was higher than that of the Ob mice (this difference was highly significant), and serum levels for insulin was within normal limits. Microscopically, hypertrophy and hyperplasia of the islets of Langerhans were found only in the pancreas of Ob mice. The increase in the number of A-cells and the decrease in the number of B-cells were revealed immunohistochemically in the islets of Small-ob mice. These changes were more severe with advance of age. In the aged Small-ob mice, perivascular and periductular cell infiltration were found, but inflammatory change of islet tissue was not confirmed in any animals examined. Diabetic symptoms in Small-ob mice seems to stem from the disparity in insulin/glucagon (I/G) ratio associated with hyperglucagonemia which result from increased number of A-cells of pancreatic islets.     

Strain differences in response to acute hypoxia: CD-1 versus C57BL/6J mice.

Some mammals respond to hypoxia by lowering metabolic demand for oxygen and others by maximizing efficiency of oxygen usage: the former strategy is generally held to be the more effective. We describe within the same species one outbred strain (CD-1) that lowers demand and another inbred strain (C57BL/6J) that maximizes oxygen efficiency to markedly extend hypoxic tolerance. Unanesthetized adult male mice (Mus musculus, CD-1 and C57BL/6J) between 20 and 35 g were used. Sham-conditioned (SC) C57BL/6J mice survived severe hypoxia (4.5% O(2), balance N(2)) roughly twice as long as SC CD-1 mice (median 211 and 93.5 s, respectively; P < 0.0001). Following acute hypoxic conditioning (HC), C57BL/6J mice survived subsequent hypoxia 10 times longer than HC CD-1 mice (median 2,198 and 238 s respectively; P < 0.0001). Therefore, C57BL/6J mice are both naturally more tolerant to hypoxia and show a greater increase in hypoxic tolerance in response to hypoxic conditioning. Indirect calorimetry indicates that CD-1 mice lower mass-specific oxygen consumption (V'o(2) in ml O(2).kg(-1).min(-1)) and carbon dioxide production (V'co(2) in ml CO(2).kg(-1).min(-1)) in response to HC (P = 0.002 and P < 0.0001, respectively), but C57BL/6J mice maintain V'o(2) and V'co(2) after HC. Respiratory exchange ratio and fluorometric assay of plasma ketones suggest that C57BL/6J mice rapidly switch to ketone metabolism, a more efficient substrate, while CD-1 mice reduce overall metabolic activity. We conclude that under severe hypoxia in mice, switching fuel, possibly to ketones, while maintaining V'o(2), may confer a greater survival advantage than simply lowering demand.     

Over-expression of Bcl-2 provides protection in septic mice by a trans effect

Transgenic mice that over-express B cell leukemia/lymphomas (Bcl)-2 in myeloid cells under control of the human MRP8 promoter (hMRP8-Bcl-2) or in T lymphocytes under the E micro promoter (E micro -Bcl-2) were compared with C57BL/6 control mice following cecal ligation and puncture (CLP). There was a significant difference in outcome between the hMRP8-Bcl-2 and control mice with 100% survival in the hMRP8-Bcl-2 mice vs 25% survival in the control mice. In separate experiments there was a significant difference between E micro -Bcl-2 and control mice with 87.5 and 22.2% survival, respectively. Adoptive transfer of CD11b-positive bone marrow cells from hMRP8-Bcl-2 or C57BL/6 mice to C57BL/6 mice subjected to CLP resulted in 100 and 0% survival, respectively. Adoptive transfer of CD11b-positive cells from either hMRP8-Bcl-2 or C57BL/6 mice to Rag-1(-/-) mice (no mature T or B cells) subjected to CLP resulted in survival of 87.5 and 12.5%, respectively. The hMRP8-Bcl-2 mice had significantly more neutrophils and fewer bacteria in the peritoneum compared with C57BL/6 mice 24 h after CLP. These experiments show that Bcl-2 over-expression is protective in CLP and that protection is independent of lymphocytes. We propose that over-expression of Bcl-2 in T cells or myeloid cells induce release of a molecule(s) that protects against death following CLP.     

Strain difference in expression of the adult-type polycystic kidney disease gene, pcy, in the mouse

DBA/2FG-pcy and C57BL/6FG-pcy congenic strains were established by transferring the polycystic kidney disease gene, pcy, to DBA/2 and C57BL/6 mice. We carried out pathological and hematological examinations of these strains at 4, 8, 16 and 30 weeks of age. In DBA/2FG-pcy mice more than 8 weeks of age, macroscopic renal cysts were observed on the surface of both kidneys. Their kidneys weight was significantly greater than in DBA/2 mice at all ages examined. Microscopic renal cysts were evenly distributed at 4, 8 and 16 weeks of age. At 30 weeks of age, the kidneys were filled with numerous polycysts. In C57BL/6FG-pcy mice, no macroscopic renal cysts were found until the animals were 30 weeks old, and the weight of their kidneys was greater than in B6 mice of the same age. From 8 weeks of age on, a limited number of microscopic renal cysts was observed, and many renal cysts were found adjacent to the enlarged Bowman's capsules. With age, the red blood cell count and hematocrit level decreased while the platelet count increased in both strains, with greater changes occurring in DBA/2FG-pcy mice than in C57 BL/6FG-pcy mice. These findings demonstrate that polycystic kidney disease exhibits strain differences in animals with a DBA/2 and C57BL/6 background. Our results suggest that phenotypic expression of the pcy gene in the mouse depends on genetic background, and that variations in the severity of human polycystic kidney disease may be explained, at least in part, by individual differences in genetic background.     

Inheritance of hydronephrosis in the inbred mouse strain DDD

The mode of inheritance of hydronephrosis was investigated by crossing inbred DDD mice having a high incidence of hydronephrosis and C57BL/6 mice having normal kidneys. In the males, incidences of hydronephrosis in F1 animals were intermediate between the two parental strains at a rate of 32.6% in (DDD x C57BL/6)F1 and 23.4% in reciprocal F1. The same tendency was observed in F2 male animals. In BCF1 males, the number of affected mice was higher in (C57BL/6 x DDD) F1 x DDD (72.4%) than in (DDD x C57BL/6)F1 x C57BL/6 (11.1%). A few affected mice were found among the females of hybrids F1, F2 and BCF1. These results suggested that hydronephrosis in the DDD strain of mice was controlled by polygenes, and that male hormones may have some effect on the occurrence of hydronephrosis.     

Targeting Apoptosis Signalling Kinase-1 (ASK-1) Does Not Prevent the Development of Neuropathy in Streptozotocin-Induced Diabetic Mice

Apoptosis signal-regulating kinase-1 (ASK1) is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K) which lies upstream of the stress-activated MAPKs, JNK and p38. ASK1 may be activated by a variety of extracellular and intracellular stimuli. MAP kinase activation in the sensory nervous system as a result of diabetes has been shown in numerous preclinical and clinical studies. As a common upstream activator of both p38 and JNK, we hypothesised that activation of ASK1 contributes to nerve dysfunction in diabetic neuropathy. We therefore wanted to characterize the expression of ASK1 in sensory neurons, and determine whether the absence of functional ASK1 would protect against the development of neuropathy in a mouse model of experimental diabetes. ASK1 mRNA and protein is constitutively expressed by multiple populations of sensory neurons of the adult mouse lumbar DRG. Diabetes was induced in male C57BL/6 and transgenic ASK1 kinase-inactive (ASK1n) mice using streptozotocin. Levels of ASK1 do not change in the DRG, spinal cord, or sciatic nerve following induction of diabetes. However, levels of ASK2 mRNA increase in the spinal cord at 4 weeks of diabetes, which could represent a future target for this field. Neither motor nerve conduction velocity deficits, nor thermal or mechanical hypoalgesia were prevented or ameliorated in diabetic ASK1n mice. These results suggest that activation of ASK1 is not responsible for the nerve deficits observed in this mouse model of diabetic neuropathy.     

Strain differences of ether susceptibility in mice

The susceptibility to ether in the following six strains of mice was tested: C57BL/6, DBA/2, BALB/c, C3H/He, ICR and ddY. Mice of 4 weeks old were exposed to a flow of air containing various concentrations of ether for 90 min and the mortalities were assessed. The C57BL/6 strain was the most resistant and the C3H/He strain was the most sensitive to the lethal effect of ether. The susceptibilities of the closed colony mice, ICR and ddY, were intermediate between those of C57BL/6 and C3H/He mice. The DBA/2 and BALB/c strains were more sensitive than these closed colony mice and made up a sensitive group with the C3H/He strain. The LD50 values for ether in male mice of C57BL/6 and C3H/He were 6.0 and 3.1% atm, and in female mice of these strains were 6.6 and 3.2% atm, respectively. The ED50 value of ether which was accompanied by loss of righting reflex after exposure for 10 min was also higher in male C57BL/6 mice than in male C3H/He mice.     

Genotype modulates the aggression-promoting quality of progesterone in pregnant mice

During late pregnancy, female mice of the DBA/2J inbred strain are more likely to exhibit aggressive behavior toward a standard stimulus intruder male than C57BL/6J females. This strain difference can not be accounted for by differences in circulating levels of progesterone (P) since pregnant DBA/2J and C57BL/6J females exhibit similar patterns of the steroid throughout pregnancy. Upon receiving subcutaneously implanted Silastic capsules containing P, virgin DBA/2J mice are more likely than virgin C57BL/6J to respond to the steroid by exhibiting aggression. Strain differences in the aggressive behavior exhibited by pregnant mice may be related to genotype-based variation in central neural tissue sensitivity to P.     

Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice

Colorectal distension (CRD) is a well-characterized model of visceral nociception, which we adapted to the mouse. CRD reproducibly evoked contractions of the abdominal musculature [visceromotor response (VMR)], which was graded to stimulus intensity. The magnitude of VMR was greater in male C57BL6 and female 129S6 mice than in male 129S6 and B6.129 mice. In 129S6, C57BL6, and B6.129 mice strains, VMR was reduced dose dependently by morphine (1-10 mg/kg) and by the kappa-opioid agonist U-69593 (0.2-2 mg/kg), although U-69593 was significantly less potent in C57BL6 mice. In additional experiments, the VMR was recorded from adult male 129S6 mice before and after intracolonic administration of various irritants. Only 30% ethanol significantly enhanced responses to CRD. The colon hyperalgesia persisted for 14 days and was associated with a significant shift of the morphine dose-response function to the left. We believe this will be a useful model for study of visceral nociception and hyperalgesia, including studies of transgenic mice with mutations relevant to pain.     

Clinico-pathological studies on small obese mice occurring in C57BL/6J-ob/ob mice

Eight small obese mice, 10 to 79 weeks of age, which occurred in C57BL/6J obese mice, were examined clinico-pathologically. These mice were characterized by small-sized obesity, and showed hyperglycemia without hyperinsulinemia and glucosuria without ketonurina throughout their life span. Morphologically, neither hypertrophy nor hyperplasia were found in the islets of Langerhans. There were an increase of A cells and a decrease of B cells in their islets. In the kidney, thickening of mesangial matrix in glomeruli and deposition of glycogen in the nucleus of epithelial cells of the distal tubules were seen. These findings suggest that the small obese mice are an obese-diabetic animal of different type from the usual obese mice (C57BL/6J-ob/ob). The mechanism for development of this condition was unknown.     

The role of the androgen receptor in anabolic androgenic steroid-induced aggressive behavior in C57BL/6J and Tfm mice

Humans self-administer anabolic androgenic steroids (AAS) at superphysiological doses for the purpose of building muscle mass and enhancing physique whereas considerably lower doses of AAS are prescribed in the clinic to treat a variety of disorders. A number of studies have demonstrated that individual AAS influence aggressive behavior in rats and mice, but few studies have examined the aggression-enhancing effects of combinations of AAS. Using the resident-intruder paradigm, Experiment 1 determined whether a cocktail of commonly abused AAS increased aggressive behavior in gonadally-intact male C57BL/6J mice and examined whether the androgen receptor (AR) was involved. Mice given either AAS cocktail or the cocktail and the AR antagonist, flutamide, for 6 weeks were subject to three weekly tests in which the percentage of mice that fought, the latency to initiate an aggressive event and the number of aggressive events per 5-min-fight session were recorded. In C57BL/6J mice, 6 weeks of AAS administration increased the likelihood of fighting, however, within the subset of mice that engaged in aggression, AAS did not specifically modulate the latency to fight or the number of aggressive events per fight. In addition, co-administration of flutamide only slightly altered the likelihood that mice given AAS will initiate a fight. Experiment 2 examined the aggression-promoting effects of AAS in gonadally-intact adult testicular feminization mutant (Tfm) mice, which are deficient in functional ARs. Overall, fewer Tfm mice compared to C57BL/6J mice fought in both drug conditions (vehicle or AAS). Taken together, these data suggest that given the presence of AR during development, AAS enhance adult male aggression in C57BL/6J mice through AR-independent and AR-dependent pathways. In contrast, in adult Tfm mice, the likelihood of AAS-enhanced aggression in adulthood is significantly reduced.     

Genotype modulates testosterone-dependent activity and reactivity in male mice

Adult castration significantly reduced the homecage locomotor activity of both inbred C57BL/6J and DBA/2J and outbred Rockland-Swiss (R-S) male mice. Castrated C57BL animals exhibited greater reductions in this behavior than did the other genotypes. Locomotor activity in a novel environment (reactivity) was also reduced by castration but only for inbred males. In both test situations, postcastration reductions in ambulation were prevented by implants of testosterone (T)-containing Silastic capsules. Thus, testicular hormones promote activity and reactivity in the male mouse in a genotype-dependent fashion.     

Diminished pheromone-induced sexual behavior in neurokinin-1 receptor deficient (TACR1(-/-)) mice

Studies in mice with targeted deletions of tachykinin genes suggest that tachykinins and their receptors influence emotional behaviors such as aggression, depression and anxiety. Here, we investigated whether TAC1- and TAC4-encoded peptides (substance P and hemokinin-1, respectively) and the neurokinin-1 receptor (NK-1R) are involved in the modulation of sexual behaviors. Male mice deficient for the NK-1R (TACR1 (-/-)) exhibited decreased exploration of female urine in contrast to C57BL/6 control mice and mice deficient for NK-1R ligands such as TAC1 (-/-), TAC4 (-/-) and the newly generated TAC1 (-/-) /TAC4 (-/-) mice. In comparison to C57BL/6 mice, mounting frequency and duration were decreased in male TACR1 (-/-) mice, while mounting latency was increased. Decreased preference for sexual pheromones was also seen in female TACR1 (-/-) mice. Furthermore, administration of the NK-1R-antagonist L-703,606 decreased investigation of female urine by male C57BL/6 mice, suggesting an involvement of NK-1R in urine sniffing behavior. Our results provide evidence for the NK-1R in facilitating sexual approach behavior, as male TACR1 (-/-) mice exhibited blunted approach behavior toward females following the initial interaction compared with C57BL/6 mice. NK-1R signaling may therefore play an important role in pheromone-induced sexual behavior.