SEARCH · PubMed Health

Results for “Rats, Mutant Strains”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1986

Abnormal zinc metabolism in unilateral maldescended testes of a mutant rat strain.

The status of zinc in a mutant rat strain with heritable maldescended testes was examined. In rats with unilateral maldescended testis, the ectopic testis consistently had decreased zinc content (121.0 +/- 23.0 micrograms zinc/g dry wt), while the eutopic testis had zinc content similar to that of normal rats (182.0 +/- 5.0 micrograms zinc/g dry wt). Uptake of zinc by the ectopic testis was comparable to normal. Sephadex gel chromatography showed greatly reduced zinc content of one of the endogenous zinc binding fractions with a mol wt of 30,000 of cytosol of the ectopic testis in spite of a near normal protein content. Incorporation of zinc-65 into this fraction was also shown to be greatly reduced in ectopic testis. Sodium dodecylsulphate-polyacrylamide gel electrophoresis demonstrated that a protein of 23,000 Da was greatly reduced in quantity. This 23-kDa protein in ectopic testis may play a role in reduced testicular function of the ectopic testis.

Animals↗

PubMed1988

A mutant rat strain deficient in induction of a phenobarbital-inducible form of cytochrome P-450 in liver microsomes.

Two phenobarbital-inducible forms of cytochrome P-450, P-450(PB-1), and P-450(PB-4), were purified from the liver microsomes of phenobarbital-treated rats and identified with P-450b and P-450e, respectively. It was found, however, that the content of P-450(PB-4) in the liver microsomes of a strain of SD rat, Qdj:SD, was very low even after phenobarbital-induction. The levels of the mRNAs for P-450(PB-1) and P-450(PB-4) were separately determined using Northern blot hybridization with specific oligonucleotide probes. It was found that the level of P-450(PB-4) mRNA in the livers of phenobarbital-treated Qdj:SD rats was much lower than that of phenobarbital-treated Slc:SD rats. Slc:SD rats are widely used in Japanese laboratories. Genetic analysis using the crossbred animals between Qdj:SD and Slc:SD rats showed that the low expression of P-450(PB-4) in Qdj:SD rats is a recessive trait and is caused by a single gene mutation. However, no difference in the 5' flanking region in P-450(PB-4) gene was found between Qdj:SD rats and Slc:SD rats.

Animals↗

PubMed1988

Studies on the genetic linkage of bilirubin and androsterone UDP-glucuronyltransferases by cross-breeding of two mutant rat strains.

Gunn rats, which have defects in bilirubin and 4-nitrophenol UDP-glucuronyltransferases (GT), were crossed with LA Wistar rats with a defect in androsterone GT. The F1 hybrids showed normal GT activities towards androsterone, bilirubin and 4-nitrophenol, demonstrating that Gunn and LA ('low activity') Wistar rats inherit a homozygous dominant trait for androsterone GT and bilirubin GT respectively. The F2 progeny showed four different combinations of bilirubin and androsterone GT activities: defects in both GT activities, a single defect in bilirubin GT activity, a single defect in androsterone GT activity and two normal GT activities. They were segregated in the approximate ratio of 1:3:3:9, which is compatible with Mendel's Principle of Independent Assortment. These results provide evidence that androsterone GT and bilirubin GT are located on different chromosomes. In the F2 generation, defective bilirubin and 4-nitrophenol GT activities were not segregated, indicating that these two mutant genes are closely linked on the same chromosome.

Androsterone↗

PubMed1990

Maturational arrest from CD4+8+ to CD4+8- thymocytes in a mutant strain (LEC) of rat.

A mutant strain (LEC) of rats was found to have a novel defect in T cell maturation, that is, arrest of differentiation from CD4+8+ to CD4+8- but not to CD4-8+ thymocytes. FACS analyses demonstrated a deficiency in the CD4+8- T cell subset in the thymus and a marked decrease in CD4+ T cells in peripheral lymphoid organs. Expression of the T cell receptor (TCR)/CD3 complex in CD4+8+ and CD4-8+ thymocytes of LEC rats was normal. Expression of class II major histocompatibility complex (MHC) in the thymus of LEC rats was also the same as that of normal rats. These results indicate that maturational arrest occurs only in the transition pathway from CD4+8+ to CD4+8- thymocytes, and that this mutation can not be attributed to the default of expression of either TCR/CD3, CD4, or class II MHC antigen. Consequently, dysfunction of helper T cells was observed in LEC rats, while killer T cells and B cells functioned normally. Although the complete identification of the origin of this mutation requires further studies, it is hoped that such investigations will throw light on the mechanism of positive selection.

Animals↗

PubMed1989

Hepatic, intestinal and renal transport of 1-naphthol-beta-D-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia.

Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR-rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol-beta-D-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR- rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR- rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR- rat when compared with the Wistar rat. Thus, the genetic defect in the TR- rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.

Animals↗

PubMed1991

Organic anion transport study in mutant rats with autosomal recessive conjugated hyperbilirubinemia.

The EHBR is a mutant rat strain with congenital conjugated hyperbilirubinemia bred from a Sprague-Dawley rat. Transport of conjugated bilirubin, indocyanine green, and tetrabromosulfophtalein from liver to bile is severely impaired in these rats. Serum bilirubin amounts to 6.0 +/- 0.05 mg/dl (n = 4) in adult rats, with 97% conjugates. The bile flow is reduced to about 65% of the control group, whereas total bile acid in 10-min bile samples is similar. Liver histology of 10 week-old rats revealed neither intracellular pigmentation nor architectural abnormalities.

Animals↗

PubMed1991

Decrease in the specific forms of cytochrome P-450 in liver microsomes of a mutant strain of rat with hyperbilirubinuria.

Eisai-hyperbilirubinuria rats (EHBR) is a mutant originated from Sprague Dawley rats. The activities of UDP-glucuronyltransferase and drug metabolizing enzymes in EHBR were compared with those in Sprague Dawley rats as the control. The activity of aniline hydroxylase was significantly increased in liver microsomes of EHBR whereas the activity of ethylmorphine N-demethylase was found to be significantly decreased in EHBR as compared to control rats. In addition, the activity of testosterone 7 alpha-hydroxylase was increased in EHBR whereas the activity of testosterone 6 beta-hydroxylase was significantly decreased in EHBR as compared to control rats. Western blot analysis of liver microsomes of EHBR with antibodies to P-450IA2, P-450IIB1, P-450IIC11 and P-450IIIA2 showed that the amounts of P-450IIB1 and P-450IIIA2 in liver microsomes were significantly lower in EHBR than in control rats. These results indicated the form-specific alteration in the amounts of cytochrome P-450 in liver microsomes of EHBR.

Aniline Hydroxylase↗

PubMed1986

Characterization of kininogen deficiency of Brown Norway rat mutant Katholiek strain.

A deficiency in the plasma kallikrein-kinin system of Brown Norway rat mutant Katholiek strain (B/N-Ka), first reported by Damas et al. was further characterized. The prolonged activated partial thromboplastin time (APTT) of B/N-Ka rat plasma was corrected by an addition of rat HMW-kininogen, indicating B/N-Ka rat is deficient in HMW kininogen. The study of kinin-release of plasmas of the three strains of rat (B/N-Ka, B/N Ki and SD) by several kininogenases expressed that B/N-Ka rat is deficient in LMW kininogen, in addition to HMW kininogen deficiency. The plasmas of the three strains of rat were gel-filtered through Sephacryl S-200 gel and profiles of kinin-release of the fractions were examined by several kininogenases. The result demonstrated that normal rat plasma contains three kinds of kininogen (HMW and LMW kininogens, and T-kininogen), and B/N-Ka plasma contains only T-kininogen. B/N-Ka rat plasma demonstrated T-kininogen antigen but no HMW kininogen by the study of immunodiffusion using their antisera raised in rabbits.

Animals↗

PubMed1992

Aganglionosis in rodents.

The etiology of aganglionosis of the bowel remains controversial. Initial embryological studies in chicks, mice, and humans suggested the defect was in the migratory capacity of the vagal neural crest cells. This traditional theory has recently been challenged by the demonstration of a defect in the local microenvironment and the suggestion that neural crest cells migrate normally until they reach the terminal defective segment of bowel which then excludes them. To contribute to this debate we studied three rodent animal models using histological, "in vivo" (kidney capsule), and "in vitro" (tissue culture) techniques. The results suggest that there is no discernible difference between mutant and normal embryos in the early migration from the vagal neural crest to the stomach. Migration through the small bowel is normal in mutant mice, but is slowed in the rat. In both strains of mice the migration of enteric precursors into the mutant colon is slowed over an extended period of time, such that a difference between normal and mutants is evidenced well before the final aganglionic region is reached. Aganglionosis is the result either of a defect in vagal neural crest migration or in the microenvironment over an extended area of the bowel and not just in the terminal aganglionic colon. There are changes in the appearance of mutant enteric neurons in tissue culture and some alterations in the gut mesenchyme; it remains to be determined which is the primary event.

Animals↗

PubMedDate not supplied

Hereditary defect of hepatobiliary cysteinyl leukotriene elimination in mutant rats with defective hepatic anion excretion.

Hepatobiliary and renal elimination of cysteinyl leukotrienes were investigated in a mutant rat strain with a hereditary defect in the hepatobiliary excretion of conjugated bilirubin, dibromosulfophthalein and ouabain. After intravenous injection of [3H]leukotriene C4, the initial half-life of radioactivity circulating in blood was 79 +/- 15 sec (S.D.) in transport mutant rats as compared to 31 +/- 6 sec (S.D.) in normal Wistar rats. The intrahepatic leukotriene radioactivity was increased 5-fold after 1 hr in mutant rats, while the biliary elimination of [3H]leukotrienes was reduced to 1.8% of control. In normal rats, 77 +/- 7% (S.D.) of the administered leukotriene radioactivity were recovered in bile within 1 hr. The total recovery of radioactivity from bile, urine, liver, intestine, stomach, kidneys, muscular system and blood 1 hr after intravenous [3H]leukotriene C4 was 89 +/- 6% (S.D.) in normal rats and 46 +/- 4% (S.D.) in transport mutants. Enterohepatic circulation was studied after intraduodenal administration of N-acetyl-[3H]leukotriene E4, a major cysteinyl leukotriene metabolite in rat bile. In transport mutants, hepatobiliary elimination of the intestinally absorbed [3H]leukotriene was reduced to 5%, whereas urinary excretion was not significantly affected. [3H]Leukotriene metabolites in bile, liver and urine were separated by reversed-phase high-performance liquid chromatography. The proportion of N-acetyl-[3H]leukotriene E4 relative to polar leukotriene metabolites was higher in the bile of transport mutants as compared to control Wistar rats when analyzed within 30 to 60 min after intravenous injection of [3H]leukotriene C4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

[Physicochemical mechanisms of organic acid transport in the apical membrane vesicles of the cells of proximal kidney tubules in rats. II. Kinetic parameters of transport and phase state of the lipid bilayer in mutant Campbell strain rats].

The kinetics of 14C-para-aminohippuric acid (PAH) transport in the vesicles and the influence of the temperature on the initial rate of this transport were studied using a purified fraction of the apical membrane isolated from the kidney cortex of the Campbell strain rats with an autosomic recessive gene. The transport was brought about owing to the facilitate diffusion mechanism. At 36 degrees C the apparent Michaelis constant was equal to 29 mM, the maximum rate--62 nmol/min on 1 mg of protein, the inhibition constant for the PAH-transport by probenecid--1.5 mM. The temperature dependence of the initial rate of PAH-transport in vesicles and that of the rate of substrate splitting by alkaline phosphatase show the break point on the Arrhenius plot at 36 degrees C-38 degrees C. The analysis of electron magnetic resonance reveals the thermotropic transition at temperatures near 30 degrees-35 degrees C. Therefore the affinity of the carrier to its substrates in vesicles of the Campbell strain rats is strongly reduced and the lipid layer is more viscous than in the normal rats. We decide therefore that the mutation taking place in the Campbell strain leads to pleotropic membrane reconstructions in different organs (eye, kidney). The discovery of such a mutation is of considerable biological interest and promotes bases for development of the membrane biochemical genetics.

Aminohippuric Acids↗

PubMed1986

Hepatic microcirculation in Zucker fatty rats.

We have developed a microscopic analyzing system for studying in vivo hepatic microcirculation, and measured the sinusoidal erythrocyte flow velocity simultaneously in the various sinusoids. With this system and organ reflectance spectrophotometry, the pathophysiological role of microcirculation and of energy metabolism in Zucker fatty rats were studied. The results were as follows: The erythrocyte flow velocity in the predominant sinusoids in the fatty rats was similar to that of the control rats, but the intersinusoidal erythrocyte flow was undetected in the fatty liver. Index of regional hepatic blood volume, regional hepatic blood flow and oxygen saturation of Hb decreased significantly in the fatty rats. The estimated in vivo oxygen consumption was not changed in the fatty liver. From these data, it is concluded that in Zucker fatty rats a marked fatty infiltration causes a decreased hepatic tissue blood flow and volume, but relatively homogeneous erythrocyte flow with an increased extraction of oxygen compensated the decreased vascular beds and maintained normal energy metabolism.

Animals↗

PubMed1990

Mast cells and fibrosis in compartments of lymph nodes of normal, gnotobiotic, and athymic rats.

Reports vary on the amount and distribution of mast cells in lymph nodes. We analysed the mast-cell population in compartments of nodes of diverse sites, from euthymic and athymic animals of various ages. Nodal mast cells were few in young animals, occurring mostly in medullary sinuses. Aging is often accompanied by a moderate increase of nodal mast cells. In compartments of a few nodes of some aged athymic and euthymic animals, the mast cells were greatly increased in the extrafollicular zone overlying medulla directly. In certain cases, this great increase was accompanied by pronounced mast-cell degranulation and by fibrosis in the mast cell-rich extrafollicular zone. It is suggested that the mast cells of medullary sinuses relate to non-immunological events, while those of the lymphoid parenchyma relate to elements that can induce humoral immune responses or are somehow involved in nodal processes of such responses. It is further suggested that an occasional emergence, with aging, of a deficiency of particular humoral immune responses may induce an excessive increase of cortical mast cells, and that activities of the resulting dense mast-cell population contribute to the onset of fibrosis.

Age Factors↗

PubMed1988

Histochemical heterogeneity of dermal mast cells in athymic and normal rats.

Mucosal mast cells (MMC) and connective tissue mast cells (CTMC) of the rat contain different proteoglycans, which can be distinguished using histochemical methods. The chondroitin sulphate proteoglycan of the MMC, unlike the heparin of the CTMC, does not show fluorescent berberine binding, is susceptible to aldehyde fixatives and stains preferentially with Alcian Blue in a staining sequence with Safranin. The majority of the dermal mast cells are typical CTMC and are located in the deep part of the dermis. Subepidermal mast cells are comparatively few in normal rats but numerous in athymic rats and mice. These cells differ from other dermal mast cells in that they stain preferentially with Alcian Blue and they appear to contain little histamine. We examined some of the histochemical properties of the skin mast cells of female PVG-rnu/rnu rats and their heterozygous littermates aged from 5 to 29 weeks. The thiazine dye-binding of the subepidermal mast cells was partially blocked by formaldehyde fixation and only about half of them showed a weakly fluorescent berberine binding. The critical electrolyte concentration of the Alcian Blue staining of the subepidermal mast cells was between that of CTMC and MMC. Deaminative cleavage with nitrous acid abolished the staining of all skin mast cells, while that of the MMC was unaffected. There were no statistically significant differences in the staining patterns of the dermal mast cells between different ages or groups of rat. These results indicate that the subepidermal mast cells contain a heparin proteoglycan which is, however, different from that of the typical CTMC of other sites. They thus appear to represent a second example of a mast cell within a defined anatomical location exhibiting a distinct proteoglycan expression.

Animals↗

PubMed1991

Liver and muscle-fat type glucose transporter gene expression in obese and diabetic rats.

In order to investigate the regulation of glucose transporter gene expression in the altered metabolic conditions of obesity and diabetes, we have measured mRNA levels encoding GLUT2 in the liver and GLUT4 in the gastrocnemius muscle from various insulin resistant animal models, including Zucker fatty, Wistar fatty, and streptozocin(STZ)-treated diabetic rats. Northern blot analysis revealed that GLUT2 mRNA levels were significantly (P less than 0.001) elevated in 14 wk Zucker fatty and Wistar fatty rats relative to lean littermates but were similar in these two groups at 5 wk of age. Furthermore, there was significant increase (P less than 0.01) in GLUT2 mRNA levels in STZ diabetic rats at 3 wk after treatment. GLUT4 mRNA levels were not significantly different between control and insulin resistant rats in all animal models. These results indicate that neither hyperinsulinemia nor hyperglycemia affects GLUT4 mRNA levels in the muscle. However, GLUT2 mRNA levels in the liver were elevated in obesity and diabetes, although this regulatory event occurred independently from circulating insulin or glucose concentrations.

Animals↗

PubMed1990

Relationship between uptake of norepinephrine by hypothalamic homogenates and the activity of brown adipose tissue.

It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5'-diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [3H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis.

Adipose Tissue, Brown↗

PubMed1988

Variations of liver prolactin receptors during the estrous cycle in normal rats and in the genetically hypoprolactinemic IPL nude rat.

Ovine prolactin (oPRL) binding to liver membranes was studied during the estrous cycle in normal and in genetically hypoprolactinemic rats. Serum levels of hormones were measured by radioimmunoassay and prolactin (PRL) binding was determined using 125I-ovine PRL in the 100,000 X g pellet. Scatchard plots obtained were curvilinear throughout the estrous cycle in the normal rat. They were analyzed in reference to the co-operativity model and to the Hill model which give the factor delta and Hill's coefficient (nH), respectively. During the estrous cycle, delta values varied from 3.77 +/- 0.66 on the day of estrous to 13.48 +/- 1.34 on the day of proestrus at 16.00 h. At the same time, nH were 0.97 +/- 0.033 on the day of estrus and 0.72 +/- 0.025 on the day of proestrus at 16.00 h. On the other hand, the number of PRL receptors did not change significantly throughout the estrous cycle. Moreover, the dissociation of 125I-oPRL from its receptor was accelerated by the presence of native ovine oPRL. These results suggest the presence of a negative co-operativity which reached a maximum on the day of proestrus in the normal rat. This co-operativity during the estrous cycle was not found in liver from genetically hypoprolactinemic (IPL nude) rats, which present a total absence of lactation. The delta values did not vary significantly and were 6.52 +/- 1.30 on the day of estrus and 4.41 +/- 0.52 on the day of proestrus at 16.00 h. The difference between the two rat strains was statistically significant on the day of proestrus at 16.00 h for both delta and nH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Variations of liver prolactin receptors during pregnancy in normal rats and in the genetically hypoprolactinemic IPL nude rat.

Ovine prolactin (oPRL) binding to liver membranes was studied during pregnancy in normal and in genetically hypoprolactinemic rats. Prolactin (PRL) binding was determined using 125I-oPRL in the 100,000 x g pellet. Scatchard plots obtained changed throughout the pregnancy in the normal rat, being almost linear from days 2 to 10, becoming curvilinear (convex) on day 16, and linear again at the end of pregnancy. They were analyzed with reference to the co-operativity and Hill models, which give delta and nH, respectively. During pregnancy, delta values varied and were respectively 2.48 +/- 0.66, 1.84 +/- 0.64, 0.52 +/- 0.06 and 1.69 +/- 0.25 on days 3, 10, 16 and 22, and the delta value on day 16 was significantly different from other days; the nH value estimated on day 16 was 1.10 +/- 0.031. These results suggest the presence of a positive co-operativity on day 16 of pregnancy. Over the same period, a huge increase in the capacity occurred on day 10 and reached a maximum on day 14. It remained elevated until the day before parturition. In the IPL nude rat, the delta value (0.92 +/- 0.45) on day 16 was significantly different from that of normal rats and indicated an absence of positive co-operativity on this day in the IPL nude rat liver. This finding was confirmed by an nH value (0.99 +/- 0.39) close to 1. The PRL-binding capacity was similar to that of normal rats, except on day 14, where it was significantly decreased. These results are discussed in relation to hormonal variations during pregnancy, particularly with regard to serum PRL and placental lactogen values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗