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PubMed1977

Effect of diet restriction on some key enzymes tryptophan-NAD pathway in rats.

Dietary intake of rats was restricted by feeding varying amounts of a 20% protein diet. After 6 weeks of feeding, some key enzymes of the tryptophan and nicotinic acid-NAD pathway, liver nicotinamide nucleotide concentration, and urinary metabolites of tryptophan and nicotinic acid were studied. With an increase in diet restriction, liver tryptophan oxygenase (EC 1.13.1.12) activity increased. Quinolinate phosphoribosyltransferase (EC 2.4.2.a) activity, on the other hand, was found to decrease with moderate diet restriction up to 50% restriction, but increased again with more severe diet restriction in rats fed 25% of ad libitum intake. Liver nicotinate phosphoribosyltransferase (EC 2.4.2.11) activity was also observed to decrease with moderate diet restriction and did not further change when the restriction was severe while picolinate carboxylase (EC 4.1.1.45) activity increased significantly only in severe diet restriction. In rats fed 25% of ad libitum intake, urinary quinolinic acid excretion was low whereas N'-methylnicotinamide excretion was elevated. Alterations in the enzyme activities accompanied by changes in the levels of urinary metabolites, observed in the present study, suggest that the potential efficiency of conversion of tryptophan to nicotinamide nucleotides is not constant and is influenced by dietary intake.

Animals↗

PubMed1987

Genetic differences in effects of food restriction on aging in mice.

Lifelong food restriction to two-thirds of normal ad libitum consumption extended mean and maximum life spans more than 200 d in male B6CBAF1 hybrid mice, already a long-lived genotype. The following biological systems were improved by food restriction, with values for older mice being similar to those previously found for younger individuals: tight wire clinging, a measure of neuromuscular performance; open field movement, a measure of voluntary activity; tail tendon denaturation rate, a measure of collagen solubility; urine concentrating ability, a measure of renal function, and hair regrowth rate, a measure of the frequency of hair follicle cycling. However, wound healing was slower in food-restricted mice than in ad libitum-fed controls. The same food restriction treatment had entirely different effects on longevities of a different genotype, male B6 (C57BL/6J) mice, reducing mean and maximum life spans 265 and 27 d, respectively. This surprising deleterious effect was not predicted by tests of tight wire clinging, open field movement and tail tendon denaturation, but was predicted by hair regrowth rates, as these were lower in restricted B6 mice than in fed controls. In genetically obese (ob/ob) B6 mice, food restriction extended mean and maximum longevities 327 and 440 d, yet no biological systems tested performed better than those of food-restricted normal (+/+) mice whose life spans were reduced. Thus the food restriction regimen that increased longevities for individuals of two genotypes decreased them for individuals of a third genotype tested in the same set of experiments.

Aging↗

PubMed1990

Effects of dietary restriction on age-related immune dysfunction in the senescence accelerated mouse (SAM).

The effects of age and dietary restriction on immune response were investigated using an animal model of accelerated senescence (senescence accelerated mouse, SAM). The experimental groups consisted of control (ad libitum fed) and restricted groups (fed 60% of energy intake of the controls). Spleen weight and total number of splenic cells were significantly lower in the food-restricted group at 8 mo of age. Percentages of T (Thy-1.1+) and B (surface Ig+) cells in the splenic cells were not significantly different between the two groups. The number of direct hemolytic plaque-forming cells per 10(6) spleen cells 4 d following immunization with sheep red blood cells and dinitrophenyl-Ficoll was significantly greater in the 8-mo-old mice in the food-restricted group than in the control group. In the latter group, antibody responses Progressively decreased with age. Mitogen responses to concanavalin A and lipopolysaccharide were maintained in the food-restricted group but were depressed in the control group at 8 mo. In addition, though autoantibody to single-stranded DNA increased in the control group with advancing age, there was a steady decrease in the food-restricted group until 8 mo. Serum immunoglobulin (IgA and IgM) concentrations were significantly lower in the food-restricted group than in controls at 8 mo of age. Therefore, our results suggest that when senescence accelerated mice are subjected to food restriction, there may be a modulatory effect on the immune dysfunction associated with advancing age.

Aging↗

PubMed1990

Effects of energy restriction on mouse mammary tumor virus mRNA levels in mammary glands and uterus and on uterine endometrial hyperplasia and pituitary histology in C3H/SHN F1 mice.

We investigated the effects of energy restriction on the pituitary-ovarian axis and on a hormone responsive gene, the mouse mammary tumor virus (MMTV). Female C3H/SHN F1-hybrid mice, known to display a high incidence of mammary tumors, ate an energy-restricted diet (48 kcal/wk) or a control diet (95 kcal/wk) beginning at the time of weaning. By 67 wk of age, 12 of 32 mice in the control group, but none of the 33 mice in the energy-restricted group, had developed mammary tumors. Six tumor-free mice from each group were studied in detail at 67 wk of age. All six tumor-free control mice, but none of the six energy-restricted mice, showed uterine endometrial hyperplasia at autopsy. Mice subjected to energy restriction did not display an estrous cycle. The average levels of MMTV mRNA in mammary glands and uteri were strongly reduced by energy restriction. MMTV mRNA levels in mammary glands from control mice were two orders of magnitude lower than those in mammary tumors. Energy restriction lowered the percentage of pituitary mammatropes and suppressed proliferation of mammatropes with advancing age. Energy restriction thus appeared to inhibit endometrial hyperplasia and to decrease MMTV production at the mRNA level in the mammary glands and in the uterus. These effects may be a consequence of hormonal changes originating at the pituitary-ovarian axis.

Animals↗

PubMed1992

Mitotic activity in mice is suppressed by energy restriction-induced torpor.

We monitored core body temperature by telemetry in energy-restricted (201 kJ/wk) and control (397 kJ/wk) C57BL/6 and SHN/C3H F1 mice to determine whether torpor may be involved in the suppression of mitotic activities resulting from energy restriction. The energy restriction regimen employed inhibited the development of cancer and greatly extended longevity in both these mouse strains. Male and female C57BL/6 mice subjected to energy restriction from 4 wk of age and tested at 3 mo of age became torporific (body temperature less than 31 degrees C) at ambient air temperatures of 20-22 degrees C, whereas control animals stayed euthermic (greater than 35 degrees C). Energy restriction also induced torpor in 3- and 13-mo-old SHN/C3H F1 female mice, whereas 3-, 13- and 24-mo-old control mice were euthermic. Energy restriction decreased mitotic activities to approximately 30% of control values in both jejunum and epidermis in 3-mo-old female C57BL/6 mice maintained at 20-22 degrees C. However, this suppression of mitotic activities was antagonized by housing the energy-restricted mice at 30 degrees C for 2 wk, indicating that torpor plays a substantial role in suppressing mitotic activities in energy-restricted mice.

Animals↗

PubMed1994

Obesity minimizes the immunopotentiation of food restriction in ob/ob mice.

The objective of this study was to investigate food restriction-related changes in several indices of immune competence in young (11 wk old) and adult (33 wk old) female lean (+/?) and obese (ob/ob) C57BL/6J mice. Body weight accumulation, tail length accretion and organ weights were more severely curtailed by food restriction in obese mice than in lean mice. Tail collagen denaturation time increased with age, although the magnitude was greater in obese mice, and this change was minimized by food restriction. Splenocyte mitogen responses were generally not altered with age in lean or obese mice, whereas food restriction augmented these responses in lean mice while having no effect or reducing them in obese mice. The concanavalin A and phytohemagglutinin responses of splenocytes from young and adult obese mice were greater than those for lean mice, whereas the bacterial lipopolysaccharide response was elevated only in adult obese vs. lean mice. Flow cytometric analysis of splenocytes revealed an increase in Thy-1+ cells with food restriction vs. freely fed obese and lean mice, with a proportional decrease in Ig+ cells. Percentages of CD4+ and CD8+ cells increased with food restriction in both lean and obese mice. These results suggest that genetic obesity largely eliminates the immunopotentiating effects of food restriction, although the rate of "aging" may be reduced by food restriction.

Aging↗

PubMed1995

Chronic protein restriction does not alter energetic efficiency or brown adipose tissue thermogenic capacity in genetically obese (fa/fa) Zucker rats.

Attenuated regulatory thermogenesis in genetically obese (fa/fa) Zucker rats involves an impaired capacity to increase sympathetic drive to brown adipose tissue in response to dietary stimuli. Young, growing lean rats fed a low protein diet reduce energetic efficiency to compensate for elevated energy intake; however, it is not known if obese rats adapt similarly to chronic protein restriction by decreasing energetic efficiency and whether this would be accompanied by increased brown adipose tissue thermogenic capacity. Lean (Fa/Fa) and obese Zucker rats were either protein-restricted (protein 8% of total energy) or fed a control diet (21% protein) starting at age 5 wk. At 9 wk, oxygen consumption (VO2) was measured in response to an intubated meal of mixed macronutrient composition. Mass-adjusted food intake (i.e., food intake/body weight 0.67) was greater in protein-restricted than in control lean rats, but not different due to diet in obese rats. Mass-adjusted brown adipose tissue uncoupling protein levels were more than 100% greater in protein-restricted vs. control lean rats, but not different between protein-restricted and control obese rats. The uncoupling protein level was not significantly different in control lean vs. obese rats. Energetic efficiency was 40% lower in protein-restricted vs. control lean, but not different in obese rats; however, the efficiency of protein utilization was significantly greater in obese protein-restricted than in obese control rats. Meal-induced energy expenditure (VO2) did not differ significantly due to diet or genotype. In conclusion, protein restriction led to overfeeding in lean rats which appeared to enhance brown adipose tissue thermogenic capacity and decrease energetic efficiency. Protein efficiency increased to more than two times its original value in obese (fa/fa) rats, but otherwise no metabolic accommodation in the capacity for regulatory thermogenesis was observed in this genotype.

Adipose Tissue↗

PubMed1995

Pre- and postweaning food restrictions interact to determine reproductive success and milk volume in rats.

This study was designed to determine if nutrient availability during gestation and early life modifies the effects of subsequent dietary intake on reproductive and lactation performance. Rat pups, whose mothers had been allowed free access to food or were food-restricted to 50% of ad libitum consumption were assigned to free access or food restricted groups after weaning, creating 4 groups (pre- and postweaning diet). Pre- and postweaning diets interacted significantly to influence age at conception, number of pups born, and milk yield on d 14 of lactation. Early undernutrition deterred conception in dams later allowed free access to food and resulted in fewer pups born to dams later allowed free access to food, but not those in the food-restricted group. By d 15 of lactation, only dietary treatment after weaning influenced litter weight. Milk yield per gram dam weight was not impaired in the food restricted-ad libitum group but was lowered in dams in the ad libitum-food restricted group. Milk yield per gram litter weight was not impaired in ad libitum-food restricted dams but was reduced in food restricted-ad libitum dams. These results extend to the preweaning period our previous finding that past or current food restriction impairs reproductive success and decreases milk yield in rats.

Animals↗

PubMed1997

Moderate food restriction affects skeletal muscle and liver growth hormone receptors differently in pigs.

The present study was conducted to determine the influence of food restriction on growth hormone receptor (GHR) in porcine skeletal muscle (longissimus dorsi and trapezius) and liver in relationship to plasma growth hormone binding protein (GHBP). At 76 d of age, pigs were allotted to one of three groups. In Group R100kg-196d, pigs were fed 70% of control food intake and slaughtered at 100 kg. Control pigs had free access to food and were slaughtered either at the same weight (Group C100kg-161d) or at the same age (Group C130kg-196d) as R100kg-196d pigs. Plasma insulin-like growth factor-I concentrations tended to be lower in food-restricted pigs than in control pigs at 40 kg (P < 0.1) and 70 kg (P < 0.05). At slaughter, there were no significant differences among the three groups. In liver, 125I-labeled bovine GH specific binding was higher (P < 0.05) in food-restricted pigs than in control pigs, and GHR mRNA level was higher (P < 0.05) in food-restricted pigs than in C100kg-161d pigs. In trapezius, 125I-labeled bovine GH specific binding was lower (P < 0.05) in food-restricted pigs than in C130kg-196d pigs, and the level of GHR mRNA was higher (P < 0.01) in food-restricted pigs than in control pigs. The levels of GHR in longissimus dorsi were not affected by food restriction. The level of plasma GHBP was lower (P < 0.05) in food-restricted pigs than in C130kg-196d pigs. These data indicate that nutritional status regulates GHR in a tissue-specific manner and that there is no simple relationship between plasma GHBP and hepatic GHR in pigs.

Animals↗

PubMed1998

Moderate dietary protein and energy restriction modulate cAMP-dependent protein kinase activity in rat liver.

Very low protein diets result in a desensitization of hepatic cAMP signaling in rats, which is characterized by a loss of cAMP-dependent protein kinase (PKA) activity and type I regulatory subunit (RI). Here we have tested whether more moderate protein restriction (Trial 1) or energy restriction (Trial 2) also modulates hepatic PKA quantity and activity. In trial 1, weanling rats were allowed free access to diets containing normal protein (15%, AL-NP), moderately restricted protein (12.5%, AL-MP) and low protein (7.5%, AL-LP); in trial 2, rats were allowed free access to diet containing 15% (AL-NP) or 0.5% protein (very low protein, AL-VLP) or were energy restricted by pair-feeding a diet isonitrogenous to AL-NP but at 65% of the energy intake (ER-IN) for 14 d. Body weights were lower (P < 0.05) by d 14 in all restricted groups compared with the AL-NP group. The quantity of cytosolic RI was lower (P < 0.05) in AL-LP and AL-VLP, but not in AL-MP or ER-IN, compared with AL-NP. In contrast, there was no effect of diet on RI in the particulate fraction. RII was not changed by moderate and low protein diets in either the cytosol or particulate fraction. However, type II regulatory subunit (RII) was greater in the cytosol of ER-IN and in the particulate fraction of AL-VLP (P < 0.05) compared with AL-NP. Specific activity of PKA was lower in the cytosol and particulate fraction (P < 0.05) in the AL-VLP and ER-IN groups compared with the AL-NP group. In contrast, specific activity of PKA was maintained in cytosol from AL-LP, but lower in the particulate fraction (P < 0.05) compared with AL-NP. In summary, protein restricted-diets lower RI subunit in the cytosol; however, only in rats fed very low protein diets is this loss of RI associated with lower cytosolic PKA activity. In contrast, energy restriction lowers PKA activity in the cytosol and particulate fractions, independent of signficant reduction in RI or RII subunits. Taken together, these data indicate that moderate protein and energy restrictions have differential effects on activity and quantity of PKA.

Animals↗

PubMed2004

Dietary restriction and immune function.

Dietary restriction is beneficial in preventing a multitude of diseases, many of which may involve the immune system in their etiology. Recent reports examining dietary restriction focused on T lymphocytes and macrophages. Dietary restriction delays the onset of T-lymphocyte-dependent autoimmune disease; this may be attributed to improved antioxidant defense mechanisms, blunting shifts in T-lymphocyte subset proportions and preventing DNA mutation frequencies. The beneficial effects of dietary restriction were shown in both the CD4 and CD8 T-lymphocyte subsets as well as in various immune compartments such as the spleen, mesenteric lymph nodes, peripheral blood, thymus, and salivary glands. In contrast, dietary restriction may have negative effects on macrophage function because recent evidence showed that dietary restriction rendered mice more susceptible to peritonitis and stimulated macrophages produced lower amounts of cytokines. The application of dietary restriction regimens to humans would be difficult; however, understanding the biochemical and molecular targets of dietary restriction in the immune system may lead to the development of new dietary strategies to delay or prevent the onset of aging, cancer, and autoimmune disease.

Aging↗

PubMed1999

Effects of timing and duration of feed restriction during rearing on reproductive characteristics in broiler breeder females.

The objective of this study was to determine whether there exists a critical period during rearing when restricted feeding of broiler breeder hens can be most beneficial on subsequent egg production. Broiler breeder pullets were subjected to combinations of either ad libitum or restricted feeding during three periods before sexual maturity. Body weight gain, feed intake, and egg production were recorded. Ovary and oviduct weights were noted at age of first oviposition. At 15 and 18 wk of age and at age of first oviposition, chicken luteinizing hormone releasing hormone-I (cLHRH-I) in the median eminence and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary and plasma were determined. The results demonstrated that alternation between ad libitum and restricted feeding during rearing changed the growth curves of the birds. Feed restriction from 7 to 15 wk followed by either ad libitum or restricted feeding led to improved reproductive performance, suggesting that long-term feed restriction may not be necessary to attain good reproductive performance. The birds restricted from 7 to 15 wk of age had higher proportional weights of ovary (> or = 1.7%) and oviduct (> or = 1.58%) at age of sexual maturity. The cLHRH-I levels in the median eminence and gonadotrophin contents in the pituitary followed that of growth in response to feeding levels and timing of feeding and could be related to the timing of the onset of lay. At age of first egg, all groups had similar levels of cLHRH-I, LH, and FSH. However, no clear effect of level of feed intake or time period of restriction could be observed for plasma LH or FSH concentrations.

Animal Feed↗

PubMed2002

Effect of physical feed restriction during rearing on large white turkey breeder hens: 2. Reproductive performance.

Large White turkey breeder hens were used to evaluate the effect of three different levels of physical feed restriction on subsequent reproductive performance. The feed treatments were: 1) fed ad libitum throughout the study (CC), 2) feed-restricted from 16 to 24 wk (CR), 3) feed-restricted from 3 to 16 wk (RC), and 4) feed-restricted from 3 to 24 wk (RR). Feed restriction was implemented so that restricted-fed hens (RC and RR) achieved a 45% reduction in BW as compared to CC hens at 16 wk. From 16 to 24 wk, feed was allotted to RR and CR hens to maintain a slight increase in BW. At the completion of the respective restriction periods, hens were gradually returned to ad libitum feeding. At 30 wk of age, hens were photostimulated for a 20-wk summer season egg production cycle. Hens receiving RC and RR treatments laid significantly more eggs than did CC and CR hens for the first 5 wk of lay. However, once the house temperature increased to 26.7 to 29.4 C during 6 to 10 wk of lay, egg production of all hens decreased, resulting in a significant decrease in cumulative egg production for RR and RC hens compared to CC and CR hens. Egg and poult weights were less for RC and RR hens compared to those from CC and CR hens. In conclusion, age of breeder, season of implementation, and length of physical feed restriction have significant effects on the reproductive performance of turkey breeder hens.

Animal Feed↗

PubMed2006

Effects of feed restriction and realimentation on digestive and immune function in the Leghorn chick.

How regulatory changes of digestive and immune functions of the gut influence each other has not been sufficiently studied. We tested for simultaneous changes in the digestive physiology and mucosal immune function of the guts of White Leghorn cockerel chicks undergoing food restriction and realimentation. Chicks were assigned to 1 of 3 groups: control = fed ad libitum 7 to 17 d of age; restricted = feed restricted d 12 to 17 (at 2 restriction levels: 54 and 34% ad libitum); refed = feed restricted d 7 to 13 and then fed ad libitum d 14 to 17. Refed chicks exhibited 1 d of hyperphagy and an increase in apparent digestive efficiency following restriction (ANOVA, P < 0.001). Total small intestine mass and duodenal maltase activity differed among the groups in the order refed > control > restricted, as expected (ANOVA, P < 0.05 for both measures). In contrast, there were no significant treatment effects on our measures of gut immune structure and function, including bursa mass, spleen mass, and total IgA content of intestinal flush samples measured with standard ELISA techniques. The results of this study indicated that, during feed restriction and realimentation, some features of gut immune function are maintained unchanged in the face of regulatory changes that influence digestive functions.

Adaptation, Physiological↗

PubMed2005

Inhibition of luteinizing hormone secretion by localized administration of estrogen, but not dihydrotestosterone, is enhanced in the ventromedial hypothalamus during feed restriction in the young wether.

The ability of steroids to inhibit LH secretion is enhanced during undernutrition. To identify potential hypothalamic sites at which this enhancement may occur, we examined LH secretion in feed-restricted or fed young wethers treated with locally administered metabolites of testosterone. In experiment 1, microimplants containing crystalline estradiol-17beta (E) or cholesterol were administered via chronic guide tubes directed to the preoptic area (POA) or ventromedial hypothalamus (VMH) in fed or feed-restricted wethers. E treatment in the VMH decreased LH pulse frequency, pulse amplitude, and mean LH concentration in feed-restricted, but not fed, wethers. E may act in the POA to suppress LH under feed restriction, but definite conclusions cannot be drawn because of steroid-independent effects of feed restriction on LH pulse frequency. In experiment 2, the effect of dihydrotestosterone (DHT) in the VMH was determined. DHT administration to the VMH did not alter LH secretion in either feed-restricted or fed wethers. Thus the VMH is one site wherein E negative feedback is enhanced during feed restriction in the wether. In contrast, we found no evidence for enhanced responsiveness to androgen negative feedback within the VMH of feed-restricted wethers. We suggest that increased sensitivity within the VMH to E, but not to DHT, is important for suppressing LH secretion in undernourished male sheep.

Animals↗

PubMed1994

Adrenal axis and hypogonadotropism in the growth-restricted female lamb.

Growth retardation induced by dietary restriction in the lamb results in a decrease in LH pulse frequency and therefore in delayed puberty. Increased circulating cortisol levels have been associated with nutritional restriction in a variety of species. The current study tested the hypothesis that hyperactivity of the adrenal axis sustains hypogonadotropism in the growth-restricted lamb. Our approach was to compare the patterns and levels of circulating cortisol and LH in ovariectomized, growth-restricted (n = 8) and ad libitum-fed (n = 6) lambs. At 37 wk of age, after the growth-restricted lambs had been on the reduced diet for 31 wk, basal cortisol levels were determined hourly for 31 h. In addition, during this period, pulsatile LH and cortisol release was determined during a 4-h period (samples every 12 min). Finally, the cortisol response to a physiologic ACTH stimulus and an audiovisual stimulus (barking dog for 2 min) was determined in frequent samples collected during the last 5 h of the 31-h period. As expected, growth-restricted lambs exhibited a low LH pulse frequency (0.25 +/- 0.10 pulses/h) compared with ad libitum-fed lambs (1.37 +/- 0.07 pulses/h). No diurnal cortisol rhythm was observed in either group, and a similar cortisol pulse frequency occurred in the two groups (1.00 +/- 0.07 pulses/h in growth-restricted lambs and 1.05 +/- 0.10 pulses/h in ad libitum-fed lambs). There was no significant difference between the groups in cortisol pulse amplitude. ACTH administration (i.v.) induced a similar cortisol pulse in 4 of 8 growth-restricted lambs and in 5 of 6 ad libitum-fed lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMedDate not supplied

Effects of a restrictive blood transfusion policy on outcomes in children with burn injury.

A restrictive blood transfusion policy decreases blood utilization and improves outcomes in critically ill adults, but the impact of a restrictive blood transfusion policy in critically ill children is unclear. The study purpose was to compare the effects of a restrictive with a traditional blood transfusion policy in children with major burn injury. A retrospective review of all blood transfusions administered in a pediatric burn center during a 5-year period was conducted. Children in the traditional group (January 1, 2000, to June 30, 2002), were transfused at a hemoglobin level of less than 10 g/dl. Children in the restrictive group (January 1, 2003, to June 30, 2005, 6 months after the adoption of a restrictive protocol) were transfused at a hemoglobin level of less than 7 g/dl. Patient groups were compared for demographics, ventilator requirements, blood transfusion number, transfusion costs, and outcomes. Of the 1140 patients studied, 266 (24%) received a total of 2577 units of blood. There was no difference in age, TBSA burn, sex, inhalation injury, or mortality between groups. Patients in the traditional group received more blood than the restrictive group (12.3 +/- 1.8 vs 7.2 +/- 1.2 units/patient, P < .001). The mean cost of blood per patient was $2781 for the traditional group and $1489 for the restrictive group. A restrictive transfusion policy in children with burn injury decreases the amount of blood transfused, does not adversely impact patient outcome, and results in significant cost savings to the institution.

Blood Transfusion↗

PubMed1991

Analysis of Fv-1 restriction in two murine embryonal carcinoma cell lines and a series of differentiated derivatives.

We have used antibiotic-resistant retrovirus vectors rescued by Fv-1-sensitive murine leukaemia viruses (MuLV) to examine the Fv-1 phenotype of two undifferentiated embryonal carcinoma (EC) cell lines derived from teratocarcinomas of mouse strain 129. In addition, a set of EC cell-derived differentiated cell lines was analysed. Restriction of both B-tropic and endogenous N-tropic virus is characteristic of the Nr-type restriction reported in mouse strain 129. However, results indicate that Fv-1 restriction is not expressed in the PCC4.aza1R EC cell line. In contrast, the F9 EC cell line showed a strong restriction of the B-tropic pseudotyped vector but failed to restrict endogenous N-tropic pseudotypes. The Fv-1 gene thus seems to be differentially expressed in two EC cell lines derived from the same mouse strain. Furthermore, the selective restriction of B-tropic but not endogenous N-tropic MuLV in F9 cells suggests that these activities function independently of each other. Analysis of PCC4.aza1R-derived differentiated cell lines revealed that three fibroblast cell lines derived by retinoic acid-induced differentiation were also phenotypically silent for Fv-1. However, a pre-adipocyte line established following simultaneous exposure to retinoic acid and 5-azacytidine showed strong restriction of both B-tropic and endogenous N-tropic MuLV. Although additional data suggest that there is no correlation between the differentiated pre-adipocyte phenotype and Fv-1 expression, our results nonetheless show that Nr restriction can be observed in some derivatives of PCC4.aza1R cells, presumably by activating expression of the Fv-1 gene.

Animals↗