Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 1. Euthymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, of euthymic rat strains in which the nude mutation had been introduced. From 10 institutes, we sampled 12 groups of euthymic rats at ages of 1 1/2-2 months and 1/2 year. We analyzed weight of body, spleen and thymus; antibody response and delayed-type hypersensitivity response to ovalbumin immunization; and (immuno)histopathology of spleen, lymph nodes, and lymphoid tissue along the gastrointestinal tract. In the spleen morphometric analysis was done of the periarteriolar lymphocyte sheath (using the antibody R73 recognizing the alpha beta-T-cell receptor) and of the red pulp (using the antibody ED2 recognizing red pulp macrophages). For almost all parameters tested, statistically significant differences between the groups (origin of the animals) were observed. A cluster analysis on the basis of body weight, spleen weight, and morphometric data of spleen did not yield clusters with a different composition among animals from individual groups. Based on the antibody response to ovalbumin, clustering revealed groups of "fast-and-high", "slow-and-low", and "intermediate" responders. The various groups differed in location within these clusters, i.e. the speed and extent of the immune response depends on the background euthymic strain. Considering the microbiological status assessed by serology, a variation was found both in post-infection state at entrance in the study, and in primo-infection associated with a rise in antibody concentrations during the study. These states showed no negative effect on anti-ovalbumin reactivity. Rather, the response in primo-infection to Rat Corona Virus, Sendai Virus, and Pneumonia Virus of Mice was the highest in animals clustered as "fast-and high" responders to ovalbumin.

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 2. Athymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, in congenitally athymic rat strains. From 11 institutes around the world, we sampled 15 groups of animals at ages of 1 1/2-2 months and 1/2 year. The analysis included weight of body and spleen; antibody response and delayed-type hypersensitivity response after immunization with ovalbumin; and (immuno)histology of spleen, lymph nodes and lymphoid tissue along the gastrointestinal tract. Morphometric analysis was done for alpha beta-T-cell receptor-bearing cells in spleen tissue as a measure of the periarteriolar lymphocyte sheath; it was also done for splenic red pulp using the antibody ED2 recognizing red pulp macrophages. For almost all variables analyzed, statistically significant differences between the groups were observed. The extent of alpha beta-T-cell receptor-bearing cells in the spleen increased with age. The functioning of these cells in immunological responses can be questioned, because an immune response to ovalbumin was invariably absent. But secondary follicles with germinal centers, reflecting T-cell-dependent B-cell reactivity, were observed in lymph nodes and Peyer's patches (up to 40% and 75%, respectively, depending on the group), with a higher prevalence in older animals. A cluster analysis on the basis of body and spleen weight and composition of spleen compartments did not yield clusters with a different profile in regard to the animals' group of origin. The data presented are useful when comparing studies performed with various athymic rat strains at different institutes.

Thyroid hormones and the hepatic handling of bilirubin. I. Effects of hypothyroidism and hyperthyroidism on the hepatic transport of bilirubin mono- and diconjugates in the Wistar rat.

The effects of thyroidectomy and of thyroid hormone administration on the hepatic transport of endogenous bilirubin were investigated in the Wistar R/APfd rat. Hypothyroidism resulted in an enhanced hepatic bilirubin UDP-glucuronosyltransferase activity and in a decreased p-nitrophenol transferase activity. It caused a cholestatic condition with a 50% decrease in bile flow and bile salt excretion, and an increased proportion of conjugated bilirubin in serum. The biliary output of unconjugated and monoconjugated bilirubins decreased in parallel by about 65%, whereas the excretion rate of the diconjugate dropped by only 47%, resulting in an increased di- to monoconjugate ratio in bile. Hyperthyroidism was characterized by a decreased bilirubin and an increased p-nitrophenol transferase activity, and by an augmented bilirubin output in bile. The output of unconjugated and monoconjugated bilirubins increased in parallel by about 50 or 100%, whereas the excretion of the diconjugate increased by only 20 to 50%, depending on the dose of thyroxine administered; this resulted in a decreased di- to monoconjugate ratio in bile. A linear positive relationship was found between bilirubin UDP-glucuronosyltransferase activity and the ratio of bilirubin di- to monoconjugates present in bile or formed by in vitro incubation of liver homogenates at low concentration of bilirubin (10 to 15 microM), indicating that bile pigment composition is mainly determined by the conjugation activity in the liver. The inverse relationship observed between hepatic beta-glucuronidase activity and the ratio of di- to monoconjugates in bile warrants further investigation to analyze whether this enzyme activity also plays a possible role in the changes in bile pigment composition in hypo- and hyperthyroid rats.

The congenic normal R/APfd and jaundiced R/APfd-j/j rat strains: a new animal model of hereditary non-haemolytic unconjugated hyperbilirubinaemia due to defective bilirubin conjugation.

In this paper the production of the R/APfd-j/j strain which is congenic with the R/APfd strain is reported. The R/APfd-j/j completely lacks hepatic bilirubin UDP-glucuronyltransferase activity, as do our GUNNXR/Pfd-j/j rat strain and various other stocks of GUNN rats (j/j) described in the literature. Our recombinant inbred strain GUNNXR/Pfd-j/j was produced from non-inbred GUNN (j/j) rats. This GUNNXR/Pfd-j/j rat was used as a donor of the jaundice gene j, the R/APfd rat serving as the recipient. After eight backcross-intercross cycles (16 generations) the R/APfd-j/j strain was obtained which is congenic with the R/APfd strain. Congenicity was demonstrated by various techniques including transplantation of skin tissue, strain-specific tumour cells and hepatocytes, the mixed lymphocyte reaction, and comparison of biochemical markers. The potential of the novel inbred strain of jaundiced rat, R/APfd-j/j, and the corresponding control strain R/APfd for biochemical and clinical studies of bilirubin metabolism are briefly discussed.

Conjugation and maximal biliary excretion of bilirubin in the rat during pregnancy and lactation and during estroprogestogen treatment.

Hepatic bilirubin conjugation and excretion were investigated during pregnancy and lactation in the rat. Bilirubin uridine diphosphate-glucuronyltransferase activity was decreased by 30% in pregnant rats, both when expressed per milligram of protein or as specific activity and per unit of liver weight. Liver size increased during pregnancy, and, as a consequence, total hepatic glucuronyltransferase activity was unchanged. The biliary bilirubin output was normal in pregnant rats, and when loaded with bilirubin, the maximal output in bile for the whole liver was also normal. In lactating rats, specific glucuronyltransferase activity returned to control values, but the activity per unit of liver weight was still lower, due to the decreased hepatic protein concentration. The liver remained enlarged during lactation, and total hepatic glucuronyltransferase activity was increased, together with the maximal output of bilirubin in bile. Two weeks after delivery, hepatic bilirubin conjugation and excretion in nonlactating mothers were comparable to those of virgin females. Parallel modifications of bilirubin glucuronyltransferase assayed in vitro and of maximal biliary output of the pigment in vivo were observed in all animals studied. The output of bilirubin diconjugates in bile was decreased during pregnancy but no changes of the proportion of the mono-to diconjugates in bile were observed 2 weeks after delivery both in lactating and in nonlactating rats. The modifications observed during pregnancy could not be reproduced by treatment with beta-estradiol and progesterone. This suggests that different hormones or modifications of steroid metabolism are probably involved in the alterations of hepatic bilirubin metabolism in pregnant and lactating rats.

Inhibitory effect of interferon on the growth of spontaneous mammary tumors in mice.

Partially purified mouse interferon type I (Mu IFN-beta), crude mouse interferon type II (Mu IFN-gamma) serum, and the interferon inducer polyinosinic acid-polycytidylic acid (poly I:C) were evaluated for their effects on the growth of spontaneously occurring mammary carcinomas in BALB/c mice. As soon as their tumors had reached a palpable size (diameter: 3-5 mm), the mice received three ip injections of Mu IFN-beta, Mu IFN-gamma, or poly I:C per week for 6 weeks. A significant (fourfold to fivefold) reduction in tumor size was achieved with Mu IFN-beta (at 10(6) U/mouse), Mu IFN-gamma (at 10(3) U/mouse), and poly I:C (at 1 mg/mouse). A similar reduction in tumor size was noted when the mice were treated with cyclophosphamide (2.5 mg/mouse, three ip injections per wk for 6 wk). Treatment with Mu IFN-beta combined with Mu IFN-gamma resulted in a greater tumor growth-inhibitory effect than treatment with either Mu IFN-beta or Mu IFN-gamma alone. In addition to inhibiting the growth of primary tumors, interferon also reduced the incidence of lung metastases. However, complete tumor regression was not observed in any mouse while under interferon therapy.

[Nomenclature of laboratory animals]. / Nomenclatuur van de laboratoriumdieren

It is essential to use a correct nomenclature for laboratory animals to avoid mistakes in the strain and stock designation, just as it is important to use the correct species name. Firstly the rules of the nomenclature for inbred animals (strains) are dealt with. The strain symbol is followed by a slant line and an appropriate substrain symbol and possible additional symbols. Different types of symbols and combinations are discussed and examples are given. Next the nomenclature of the outbred animals (stocks) is treated. The code of the breeder is followed by a colon, the stock symbol and possible additional symbols.