The Bruce effect in Norway rats

Intrauterine implantation of fertilized ova can be blocked by exposing recently inseminated females with an unfamiliar male. This selective pregnancy failure, designated as the Bruce effect (Bruce, Nature 1959; 184:105), is well studied in laboratory mice and has been confirmed in several other rodent species. However, no clear information exists concerning this phenomenon in the laboratory rat. The present study was conducted to investigate whether or not the Bruce effect exists in the rat. Females of two F1 hybrid strains (n(total) = 354) with different MHC genotypes (F344BNF1, RT1(lv1/n), and LEWPVGF1, RT1(l/c)) were mated with males of their own strain and subsequently exposed during the first 4 days postcoitus either to a male of the other hybrid strain or to an unfamiliar male of the same strain as the stud. The litter rate of each treatment group was determined. As a control, mated females of both strains were reexposed to the stud male to determine baseline litter rates. Female rats of both F1 hybrid strains showed a significantly lower litter rate when exposed to males of a different strain than their stud male, compared to the expected values of birth rates observed in control females (F344BNF1: P = 0.017; LEWPVGF1: P = 0.019). In contrast, there was no difference between expected and observed litter rates in females of both F1 hybrid strains after exposure to an unfamiliar male of the same strain as their stud. Our results demonstrate for the first time that the Bruce effect, well documented in mice, occurs in the Norway rat.     

D-penicillamine-induced granulomatous hepatitis in brown Norway rats

The mechanism of idiosyncratic drug reactions (IDRs) remains poorly understood. D-penicillamine treatment is associated with a wide range of autoimmune reactions including liver injury. An animal model which utilizes brown Norway (BN) rats has been used to investigate the mechanism of D-penicillamine-induced IDRs because it mimics the autoimmune reactions that occur in humans. The purpose of this study was to investigate the type of liver injury that results from D-penicillamine treatment in BN rats. We had previously noted that D-penicillamine caused histological changes in the liver, but there was no increase in alanine transaminase (ALT), and we assumed that there was no significant injury. However, we subsequently discovered that D-penicillamine inhibits the ALT assay. In the present study, we found that treatment of BN rats with a low doses of D-penicillamine (10 or 15 mg/day) resulted in a mild increases in glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) activities; however, this was not associated with histological changes. A higher dose of D-penicillamine (20 mg/day) resulted in 63 % of the rats developing a skin rash, and these rats had elevated serum GLDH and SDH levels with histopathological changes characteristic of granulomatous hepatitis. This included large clusters of leukocytes in the form of granulomas that contained neutrophils, macrophages, and CD8 T cells. These changes did not occur in the rats that did not get sick. This model may be a good model to investigate the characteristics of drug-induced granulomatous hepatitis.     

Spontaneous immune complex orchitis in Brown Norway rats

Immune complexes occur spontaneously in the testis of Brown-Norway (BN) inbred rats between the basal lamina of the seminiferous tubules and the outer lamina of the myoid testicular cells. The deposits can be detected immunohistologically (IgG; C3) and by electron microscopy. The immune complexes appear between the 8th and 12th weeks of life, increase in amount up to the 30th week and decrease thereafter. After about the 20th week, of life, 15% of the animals show destruction of the germinal epithelium accompanied by an infiltration of lymphocytes and plasma cells. The final stage of this disease, which initially shows no signs of inflammation, is characterized by diffuse tubular atrophy. However, up to the 70th week of life, 85% of the animals with immune complexes show no pathological alterations. Antibodies eluated from the testes react with spermatocytes I and structures close to the lumen of the seminiferous tubules, but not with mature sperms. Serum antibodies to sperms occur in about 25% of the BN rats, but the presence of these antibodies shows no correlation with the immunohistological findings. This newly described spontaneous immune complex orchitis is regarded as a further example of an in-situ-induced immune complex disease. The observations made here can be compared with those in (peri-) membraneous glomerulonephritis, another example of a disorder resulting from in-situ-formation of immune deposits.     

Acute phase plasma proteins in kininogen-deficient Brown Norway rats

We examined whether Brown Norway rat plasma (BN/May Pfd f) contains alpha 1-cysteine proteinase inhibitor (alpha 1-CPI), also called major acute phase alpha 1-protein or T-kininogen. T-kininogen is a low molecular weight kininogen from which kinin can be released by trypsin but not by kallikreins. The BN plasma reacted with rabbit anti-alpha 1-CPI gamma globulins. Purified alpha 1-CPI released a kinin-like activity with trypsin and with homogenate of salivary glands, as Brown Norway rat plasma did. High concentration of added rat urine induced a small release (10%) of kinin from alpha 1-CPI. Preincubation of Brown Norway rat plasma with rabbit anti-rat alpha 1-CPI gamma-globulins nearly suppressed the kinin-forming substrate of trypsin in this plasma. These results indicated that plasma of our Brown Norway rats contains only alpha 1-CPI as kinin-forming substrate. This plasma contains low amount of alpha 2-macroglobulin, while its content in orosomucoid and haptoglobin was a little larger than that of Wistar rat plasma.     

Thermal environment affects hair coat development of Norway rats

Newborn rats have limited homeothermic capabilities and little insulation. Nevertheless, rats flourish in diverse thermal environments. We hypothesized that the environmental temperature influences the development of their hair coat insulation. Rats were housed from birth (0 d) in either a cool (17 °C), moderate (25 °C), or warm (33 °C) environment. Measures were recorded from young juveniles (22 d), old juveniles (43 d), and young adults (85 d). Cool-housed rats were found to develop greater body and coat mass and a higher coat mass to body mass ratio than warm-reared rats. These results indicate that thermal environment affects the growth of the hair coat insulation of developing rats.     

Plasma prekallikrein deficiency in a strain of Brown Norway rats

Plasma of a strain of Brown Norway rats has a prolonged partial thromboplastine time while its Quick time is normal. With kaolin, this plasma does not form kinins. These results are the consequence of a lack of plasmatic prekallikrein-like activity.     

Seoul virus infection increases aggressive behaviour in male Norway rats

In natural populations of rodents, males are more likely to engage in aggression and be infected with hantaviruses than females. Whether the relationship between hantavirus infection and aggression is due to host- or parasite-mediated mechanisms is unknown. The aim of this study was to determine whether hantavirus infection causes an increase in aggression in male rats and whether these behavioural changes are due to infection of the central nervous system or peripheral tissues. Male laboratory rats were infected with Seoul virus and tested for aggression in a resident-intruder paradigm 15 and 30 days postinoculation (p.i.). Males tested 30 days p.i. (i.e. during the persistent phase of infection) spent more time engaged in aggression than either uninfected males or males tested during the acute phase of infection (i.e. 15 days p.i.). Males that engaged in aggression for a longer duration had more virus present in lung, kidney and testis than males that spent less time engaged in aggression. Infected males shed virus in saliva, faeces, and urine; virus shedding, however, was not correlated with aggression and neither wounding nor transmission of virus to intruder males occurred during behavioural tests. Infection with Seoul virus did not alter either testosterone or corticosterone concentrations. Seoul virus antigens were not detected in the brains of infected rats. These data suggest that hantavirus infection leads to elevated aggression in infected males and may be a by-product of increased virus replication in peripheral tissues.     

Hormonal control of urine-marking in wild and domestic Norway rats

Wild and domestic Norway rats will actively urine-mark a small rod suspended across their home cage. Administration of testosterone to castrated male rats indicated that the urine-marking response is hormone dependent.     

Induction of atherosclerosis in Brown Norway rats by immunization with ovalbumin

A study was carried out to establish an animal model that would be suitable for evaluating the role of the diet in immune cell-mediated atherogenesis. Brown Norway rats were initially treated with hypervitamin D2 for 4 days and then fed on an atherogenic diet for 3 months, during which period the rats were either immunized with ovalubumin plus Al(OH)3 (OVA group) or with Al(OH)3 alone (control group) every 3 weeks. Aortic lesions were mainly composed of foam cells, the lesions evaluated by the intimal thickness of the ascending aorta being more severe in the OVA group than in the control group. The OVA group, in comparison with the control group, showed prominently increased serum levels of OVA-specific IgG and rat chymase, an indicator of mast cell degranulation. The intimal thickness was positively correlated with the level of chymase. Immunization had no effect on the serum lipid levels. These results support the hypothesis that mast cells play a role in the early stage of atherosclerosis and suggest that this animal model could be useful for evaluating the role of the diet in immune-related atherogenesis.     

Postpartum copulatory and maternal behaviour in Norway rats under seminatural conditions

Virgin female rats were mated at a freely cycling oestrus, and then again with the same males at the subsequent postpartum oestrus. Copulatory behaviour at each mating was compared and the temporal patterning of the female's mating and maternal behaviour was analysed. Postpartum females were found to conserve the number of ejaculatory series received, yet the series were shorter, resulting in a shorter time being occupied, by this mating. During mating, females spent little time with their litters, and then mainly in the post-ejaculatory intervals. Ejaculatory series were rarely disrupted by nesting. The postpartum female rat seems to engage in behavioural time-sharing.     

Airway remodeling in allergen-challenged Brown Norway rats: distribution of proteoglycans

Proteoglycans (PG) have important effects on the mechanical properties of tissues and the phenotype of various structural cells. Little is known about changes in PG deposition in the airways in animal models of asthma. We studied changes in PG in the airway wall of Brown Norway rats sensitized to ovalbumin (OA) and exposed to repeated OA challenge. Control (Sal) animals were sensitized and challenged with saline. After the 3rd challenge, animals were killed and lungs fixed in formalin. Tissue sections were incubated with antibodies to the small, leucine-rich PG, decorin, and biglycan and collagen type I. Airways were classified according to basement membrane perimeter length (< or =0.99, 1-2.99, and > or =3 mm). Decorin, biglycan, and collagen type I were increased in the airways of OA vs. Sal rats. Remodeling was most prominent in central airways. The distribution of PG differed with respect to the subepithelial vs. airway smooth muscle (ASM) vs. adventitial layer. Whereas biglycan was readily detected within the ASM, decorin and collagen were detected outside the ASM and especially in the adventitial layer. Differences in the distribution of these molecules within the layers of the airway wall may reflect their specific functional roles.