Normal Albino Mice Research Articles

Effect of desferrioxamine on the hepatotoxicity of adriamycin in normal mice

AbstractThe effect of the iron chelator, desferrioxamine (DFO) upon the hepatotoxic effects associated with the use of adriamycin as a cytotoxic agent were evaluated in normal albino mice. Hepatocellular toxicity was assessed by measuring serum aspartate transaminase (SGOT), serum alanine transaminase (SGPT) and serum alkaline phosphatase (ALP) activity. In addition, glucose‐6‐phosphatase (G‐6‐PTase) activity, nucleic acids, calcium, magnesium, and iron levels in liver tissue were also measured. Adriamycin treatment (2 mg/kg i.p.), administered every other day for a total of 5 doses produced a 2.5‐fold increase in SGOT and SGPT, while ALP activity showed a 30% increase in comparison to normal, untreated controls. However, hepatic G‐6‐PTase activity showed a significant decrease after the adriamycin treatment regimen. The calcium and iron content of liver showed also a marked decrease, while magnesium levels were increased two‐fold after treatment with adriamycin. In the presence of the iron chelator, DFO (100 mg/kg i.p., administered every other day for 5 doses), adriamycin treatment did not result in any significant changes in SGOT, SGPT, ALP, or hepatic G‐6‐PTase activity. Histopathological examination of mouse liver showed diffuse ballooning degeneration of liver cells with perivascular cellular infiltration after adriamycin treatment. In the presence of DFO, only focal cellular degenerative and minimal fatty changes were observed. The observed hepatocellular damage is believed to be a result of the lipid peroxidation induced by adriamycin. The role of DFO in preventing lipid peroxidation has been discussed. This study provides evidence that DFO may be useful for prevention of the lipid peroxidation and hepatocellular damage induced by adriamycin. © 1993 Wiley‐Liss, Inc.

Development and degeneration of retina in rds mutant mice: altered disc shedding pattern in the heterozygotes and its relation to ocular pigmentation.

In the heterozygous mutant (rds/+) mice, receptor outer segments (ROS) are irregular in form and are shed as abnormally large phagosomes. In the albino rds/+ mice, peak frequency of pigment epithelial (RPE) phagosomes is higher than normal and is recorded near the end of the light period, instead of at the time of light onset as in the normal (+/+) albino mice. In pigmented mice of both genotypes, the maximum numbers of phagosomes in the RPE remain lower than in the albinos. In pigmented +/+ mice the number of phagosomes is already high at the time of light onset. The number rises to peak after one hour and then declines slowly. The lowest frequency is reached after the end of the light period. In pigmented rds/+ mice, the number of phagosomes in the RPE is lowest at the time of light onset. The number rises rapidly to peak level within two hours, then declines and remains low until light onset. If the dark period is prolonged, phagosome frequency in the rds/+ RPE remains lower than in +/+ RPE. If the light period is prolonged, phagosome frequency in the rds/+ RPE remains at a higher level than in the +/+ RPE. This differential response to altered light regimen in the rds/+ and +/+ mice is less pronounced in the pigmented than in the albino individuals. The phagosomes in the rds/+ RPE are larger than in the +/+ RPE in all light regimens. These results show that ocular pigmentation may modify the circadian pattern of ROS disc shedding in the rds/+ retina.

Development and degeneration of retina in rds mutant mice: Altered disc shedding pattern in the albino heterozygotes and its relation to light exposure

The number of phagosomes in the retinal pigment epithelium (RPE) of normal albino mice, maintained in cyclic light, is highest at the time of onset of light. The number declines to the lowest level around the start of the dark period. If the dark period is prolonged, the pattern of shedding remains cyclic but the phagosome count is higher than normal. If the light period is prolonged the phagosome count remains low and the rise to the peak is delayed. The number of phagosomes in the RPE of albino rds/+ mice, maintained in cyclic light, peaks to higher than normal level and the peak is recorded near the end of the light period. If the dark period is prolonged the phagosome count in the RPE of rds/+ mice remains lower than in the similarly treated normal mice. The phagosome count in the RPE of rds/+ mice, exposed to a prolonged light period, remains higher than in the similarly treated normal mice. In both normal and rds/+ mice, bom and reared in total darkness, the pattern of disc shedding is very different but the rds/+ mice show a relatively higher frequency of phagosomes in the RPE than the normal mice. The phagosomes in the rds/ + RPE are larger than normal. An increase in size appears to correspond with increased rate of shedding in the rds/+ mice and to a lesser extent also in normal mice. Thus, the pattern of disc shedding in the albino rds/+ mice, which is different from the normal albino mice, also shows a different reaction to changes in the environmental light.

Effect of Ultraviolet Irradiation on Mast Cell-Deficient W/Wv Mice

The effect of UV irradiation on the skin was investigated in (WB-W/+) X (C57BL/6J-Wv/+)F1-W/Wv mice, which are genetically deficient in tissue mast cells. Their congenic littermates (+/+) and normal albino mice (ICR or BALB/c) were used as controls. Mice were irradiated with 500 mJ/cm2 of UVB and the increment of ear thickness was measured before and 6, 12, and 24 h after irradiation. Ear swelling in W/Wv mice at 12 and 24 h after irradiation was significantly smaller than that in +/+ and ICR mice. In contrast, the number of sunburn cells formed 24 h after UVB irradiation (200 or 500 mJ/cm2) was similar in W/Wv, +/+ and ICR mice. On the other hand, when mice were treated with 8-methoxy-psoralen (0.5%) plus UVA irradiation (4 J/cm2) (topical PUVA), ears of W/Wv and BALB/c mice, which were both white in color, were thickened similarly 72 h after treatment, but less swelling was observed in +/+ mice, which were black in skin color. The amount of prostaglandin D2 (PGD2) in ears, determined by radioimmunoassay specific for PGD2, was elevated 3-fold in +/+ and ICR mice at 3 h after irradiation with 500 mJ/cm2 of UVB in comparison with basal level without irradiation. However, such elevation was not observed in W/Wv mice. These results suggest that mast cells play an important role in UVB-induced inflammation, and PGs from mast cells are responsible at least in part for the development of this reaction. However, neither mast cells nor PGs contribute to the sunburn cell formation and ear swelling response by PUVA treatment.

Quantitative lung morphology in Japanese waltzing mice.

We have reinvestigated the question of whether exercise stimulates lung growth by determining body weight (BW), lung volume (LV), alveolar surface area (SA), and alveolar number (N) in Japanese waltzing mice, in their phenotypically normal littermates, and in normal albino mice. BW, LV, SA, and N were all less in waltzing mice than in their littermates; LV/BW, SA/BW, and N/BW were indistinguishable in the two groups. Age-matched albino mice had larger BW and smaller N/BW than the waltzers or their littermates. The results indicate that both waltzing mice and their nonwaltzing littermates have more highly compartmentalized lungs than albino mice of the same age. However, the data provide no support for the hypothesis that sustained exercise enhances lung growth.

Failure of XX cells containing the sex reversed gene to produce gametes in allophenic mice.

Allophenic mice have been produced by combining embryos from normal albino mice with embryos of normally pigmented mice carrying the autosomal dominent gene for sex reversed (Sxr) in order to determine the ability of XXSxr cells to differentiate either into sperm or eggs. Sixteen male and six female allophenes have thus far produced more than 1,200 offspring, none of which arose from an XXSxr primordial germ cell. Two allophenic mice were sterile hermaphrodites, and 13 others have yet to be tested. These results indicated that an XX cell is incapable of spermatogenesis even when supplied with the male determining Sxr gene, and that this gene also prevents XX cells from undergoing oogenesis. The latter result contrasts with a previous report of a functional sex reversed oocyte in the mouse.

Colchicine Administration to Mice: A Metabolic and Ultrastructural Study

Abstract. A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein‐like particles which eventually transformed into lipid droplets. These ultra‐structural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.

Colchicine administration to mice: a metabolic and ultrastructural study.

A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein-like particles which eventually transformed into lipid droplets. These ultrastructural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.

Regulation of carbohydrate and lipid metabolism in the liver and adipose tissue of normal and diabetic mice

Gluconeogenesis has been studied in perfused livers of normal albino, as well as of C57 lean and obese-hyperglycemic ( ob/ob) mice. In livers of normal albino mice, the highest rate of gluconeogenesis was observed with saturating levels of fructose and dihydroxyacetone. Pyruvate and lactate were about half as effective. Oleate-albumin complex did not stimulate gluconeogenesis. Glucagon, epinephrine or cyclic AMP did not alter gluconeogenesis, despite the fact that they were strongly glycogenolytic, suggesting that gluconeogenesis in livers of normal albino mice is regulated mostly by substrate availability. Gluconeogenesis in livers of C57 lean and ob/ob mice was compared and it was found that the capacity for gluconeogenesis from lactate or pyruvate was similar in both groups of mice. Lipogenesis from glucose was studied in C57 lean and ob/ob mice, using an in vivo technique. Lipogenesis per total liver or per total adipose tissue was extremely high in the ob/ob animals compared with the lean ones. Lean mice responded to intravenous insulin with a marked increase in lipogenesis while ob/ob mice did not. Insulin-stimulated lipogenesis in the lean animals was similar in magnitude to that of non-treated ob/ob mice. When ob/ob mice were made relatively insulin deficient by treatment with streptozotocin or anti-insulin serum, liver and adipose tissue lipogenesis were markedly decreased. It is postulated that part of the increased lipogenesis seen in the ob/ob mice may be related to their abnormally high circulating insulin levels. This view is strengthened by experiments carried out on perfused livers of C57 lean and ob/ob mice. Basal and substrate-stimulated lipogenesis, as well as newly synthesized triglyceride secretion by livers of ob/ob mice, was greater than that of lean controls. Furthermore, in the absence of oleate, the secretion of triglycerides by livers of ob/ob mice was much higher than that of lean mice but it was not stimulated by oleate, while such a stimulation could be obtained in livers of normal controls. All these anomalies of lipid metabolism could be restored towards normal when the ob/ob mice were made relatively insulin deficient by streptozotocin treatment prior to the experiments. In perfused livers of normal albino mice the release of triglycerides into the perfusate has been measured as an index of very low density lipoprotein (VLDL) secretion. Vincristine or colchicine, drugs known to interfere with the microtubular system, were found to inhibit markedly triglyceride release. Biochemical and ultrastructural evidence has indicated that these drugs affect specifically microtubules. In a similar fashion, vincristine was found to decrease the secretion of globulins, albumin and small polypeptides by perfused livers. It is concluded that the functional integrity of microtubules is important for the intracellular movement and eventual release from the liver of VLDL particles, as well as of albumin and other proteins.

RETURN TO NORMAL OF BLOOD-GLUCOSE, PLASMA-INSULIN, AND WEIGHT GAIN IN NEW ZEALAND OBESE MICE AFTER IMPLANTATION OF ISLETS OF LANGERHANS

In New Zealand Obese (NZO) mice characterised by hyperglycæmia, hyper-insulinæmia, obesity, and a diabetic lag tolerance to oral glucose, blood-glucose levels, plasma-insulin levels, body-weight gain, and glucose tolerance all returned to normal after implantation of pancreatic islets isolated from normal albino mice. Islets were shown to be viable for at least 10 weeks when implanted intraperitoneally. After removal of the implanted islets the animals revert to their original state. It seems that the genetic lesion responsible for the obese state lies within the islets of Langerhans. The adenylcyclase activity of the NZO islets is similar to those of normal albino mice. The defect within the islets is as yet unknown.

ULTRACYTOCHEMICAL DEMONSTRATION OF INTRACELLULAR AMINO GROUPS BY THE HYDROQUINONE-FERRICYANIDE SYSTEM

Ultracytochemical methods for the demonstration of reactive amino groups in the cell were presented. The method utilizes either the hydroquinoneferricyanide system or the hydroquinone-tetrazolium system.The reactive amino groups were observed in the mitochondrial matrix and probably in substances in Z in the cardiac muscle of the normal adult albino mice.

Le Auxine in Biologia Animale: Parte I - Azione dell'Acido Indolacetico e delta Kinetina in vivo, su tessuti normali e tumorali

The activity of some vegetal auxins in animal biology has been experimentally studied. A cyto- and mitokinetic action of Kinetine (6-furfurylaminopurine) was demonstrated on cells of sarcoma 180 of the rat, either by direct application or by action through the host organism. Another auxin, the indolacetic acid, was found to stimulate the proliferation of vegetal and animal cells, and to increment their mitokinetic activity. These phenomena seem to be enhanced by the association indolacetic acid-Kinetine. Researches carried out on normal albino mice parenterally treated with solutions of indolacetic acid alone, and associated with Kinetine, showed absence of acute and chronic toxicity, except for a certain degree of liver impairment due to the action of indolacetic acid. No influence was noted on the mitokinetic activity. on liver tissue, and on the cutaneous germinative layer. Similarly, the DNA synthesis in the liver tissue of animals treated with the tested auxins, appeared to be uninfluenced. In a series of albino mice inoculated with 180 ascites sarcoma, and contemporaneously treated with indolacetic acid, and indolacetic acid + Kinetine (endoperitoneal or subcutaneous route), a marked stimulation of the initial tumour development was observed, with increase of ascites and stimulation of cytokinetic and mitokinetic activity of tumour cells. This influence was more marked following endoperitoneal administration. The association of the auxins did not seem to enhance their natural activities.

Influence of the Infection upon the Reticuloendothelial System, Internal Organs, and Distribution of Circulating Leucocytes of Normal Albino Mice

Influence of the Infection upon the Reticuloendothelial System, Internal Organs, and Distribution of Circulating Leucocytes of Normal Albino Mice

Certain Affections of the Liver That Arise Spontaneously in So-Called Normal Stock Albino Mice.

ConclusionCertain pathological states which arise spontaneously in the livers of so-called normal stock mice, especially with increasing age, have been described. Of particular interest are the hepatic lesions of (a) infiltration and necrosis, and (b) of intranuclear inclusion bodies-both occurring in Rockefeller Institute and Swiss strains of albino mice. The relation of the two types of changes is still to be studied as well as their etiology.

Virus of Spontaneous Encephalomyelitis Found in Intestines of Normal Wild Gray Mice

Conclusions(1) Wild gray house-mice are as susceptible to intracerebral introduction of Theiler's virus as are albino mice. (2) Apparently normal gray mice trapped in an animal house in which almost all adult albino mice are carriers of Theiler's virus, reveal this virus in their intestines and not in their brains. (3) The virus is indistinguishable from that obtained from the intestines of normal albino mice. (4) The number of gray mice shown to be carriers of Theiler's virus, while considerable, appears to be lower than that of carriers found among the albino strain.Preliminary tests to the present time have failed to indicate that the virus is demonstrable in gray house and field mice trapped at a distance from the laboratory. This subject is still under investigation.