• Korean Journal of Animal Reproduction
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• v.22 no.2
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• pp.137-143
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• 1998

The effects of continuous GH(hGH) secretion on the female reproduction was studies in adults female transgenic rats expressing the hGH gene with a mouse whey acid protein (mWAP) promotor. Two line of transgenic female rats carrying the mWAP/hGH gene were established and used in the study. One was characterized by relatively high levels of serum hGH (high line), and the other had relatively low levels (low line). 1. High line female rats had recurring, Pseudopregancy-like estrous cycles accompanied by increased serum progesterone level for 2 weeks after ovulation, and they were fertile. 2. In the rats, luteinization occurred spontaneously without cervical stimulation, probably due to high levels of serum hGH, which has prolactin (PRL)-like activity in the rat. 3. Low line female rats had recurring, regular 4-days estrous PRL surge following cervical stimulation were not, detected and PRL secretion was not induced by a dopamine antagonist. 4. The ovarian tissue in this line had a much higher number of corpora lutea and grew much heavier than in normal littermates, suggesting impairment of PRL induced structural luteolized. Su, pp.ession of PRL secretion in the low line rats was, at least in part, due to a marked decrease in the number of lactotrophs in the pituitary. The present study shows that the serum hGH level plays a crucial role in regulating luteal function in female transgenic rats expressing the hGH gene.

• Korean Journal of Animal Reproduction
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• v.22 no.2
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• pp.127-136
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• 1998

A chimeric gene comprising murine whey acidic protein(mWAP) and human growth hormone(hGH) was used to produce transgenic rats express hGH and secrete it into the blood. Two lines of transgenic rats carrying the mWAP/hGH construct were established; High line was characterized by relatively high levels of serum hGH, and low line had relatively low levels. The secretory profiles of rat GH(rGH) as well as hGH, the transgene product, were obtained in transgenic males and females of low line; both hGH and rGH serum levels were flattened with no episodic fluctuations, and the overall mean concentration of rGH was significantly lower than in normal littermates. Although the animals of High line showed an acceles, as assessed by vaginal opening and occurrence of first ovulation, advanced by 7∼8 days in both lines of animals. Accordingly, the body weight at puberty of low line transgenic females was much lower than that of normal littermates, indicating that continuous hGH expression could induce precocious puberty without enhancing the growth rate.

• Environmental Analysis Health and Toxicology
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• v.22 no.2 s.57
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• pp.165-170
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• 2007

Elevation of homocysteine levels is a risk factor for cardiovascular diseases and liver diseases. It has been reported that both streptozotocin-induced type I diabetic rats and obese type II diabetic rats have plasma total homocysteine lower than each control rats. We determined the effects of lean type II diabetes on homocysteine levels using type 2 diabetic Goto-Kakizaki rats. The concentrations of serum glucose were increased to ${\sim}two-fold$ of control levels and the total cholesterol levels were also increased in GK rats. Hepatic aspartate, histidine, threonine, alanine and methionine levels were significantly increased in GK rats. Plasma aspartate and glutamate levels were elevated, but threonine and arginine levels were decreased in GK rats. Plasma total homocysteine levels were not changed in GK rats, but hepatic total homocysteine levels were increased to ${\sim}three-fold$ of control levels. These results suggest that hepatic metabolism of sulfur-amino acid may be altered in diabetic condition.

• Korean Journal of Animal Reproduction
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• v.22 no.2
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• pp.145-152
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• 1998

Many trials have been made to produce transgenic animals using sperm cells as a vector transferring foreign DNA into eggs, but reliable results are yet to be obtained (Brinster et al., 1989; Lavitrano et al., 1989; Bachiller et al., 1991; Sato et al., 1994). Recently, one of author(SO) demonstrated that mouse blastocysts derived from eggs fertilized by spermatozoa of male mice single injected with liposome-DNA complexes within the testis expressed thegene (Ogawa et al., 1995.) Here we report that a single injection of liposome-encapsulated DNAs into the testis of either male rats or mice resulted in successfully gene transfer to the postpartum progeny. The expression of mRNA derived from transgenes was also demonstrated in transgenic animals thus obtained. Further, the transmission of the exogenous gene to the descedants was confirmed in one line of transgenic rat up to F4 generation, indicating that the gene was stably incorporated into the germ line. Thus, direct single injection of foreign DNA into the testis provides a novel and convenient means to generate transgenic animals.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.136-136
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• 2004

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.354-360
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• 1999

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034,$ 7-carboxymethyloxy-3^{l}, 4^{l},$ 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD : two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3~3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 gm/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

• The Korean Journal of Pain
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• v.22 no.3
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• pp.210-215
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• 2009

Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit (Cav ${\alpha}2{\delta}1$) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cav ${\alpha}2{\delta}1$-mediated tactile allodynia in Cav ${\alpha}2{\delta}1$ overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cav ${\alpha}2{\delta}1$ upregulation and behavioral hypersensitivity, without and with the presence of other injury factors, respectively. Methods: The transgenic (TG) mice were generated as described elsewhere (Feng et al., 2000). The left L5/6 spinal nerves in the Harlan Sprague Dawley rats were ligated tightly (SNL) to induce neuropathic pain, as described by Kim et al. (1992). Memantine 2 mg/kg (10 ul) was injected directly into the L5/6 spinal region followed by $10{\mu}l$ saline. Tactile allodynia was tested for any mechanical hypersensitivity. Results: The tactile allodynia in the SNL rats could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5 hours. The tactile allodynia in the Cav ${\alpha}2{\delta}1$ over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5, 2.0 and 2.5 hours. Conclusions: The behavioral hypersensitivity was similar in the TG mice and nerve injury pain model, supporting the hypothesis that elevated Cav ${\alpha}2{\delta}1$ mediates similar pathways that underlie the pain states in both models. The selective activation of spinal NMDA receptors plays a key role in mediating the pain states in both the nerve-injury rats and TG mice.

• YAKHAK HOEJI
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• v.53 no.2
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• pp.74-77
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• 2009

Food deprivation decreases hepatic glutathione (GSH) levels, which is ascribed to alterations in availability of hepatic cysteine, a rate limiting factor for the GSH synthesis. The present study examines the effects of food deprivation on hepatic metabolism of sulfur amino acid in male rats. In rats fasted for 24 or 48 hours, hepatic GSH levels were decreased from $6.70{\pm}0.16{\mu}mol/g$ liver to $4.02{\pm}0.20$ or $4.06{\pm}0.07{\mu}mol/g$ liver, respectively. Hepatic S-adenosylmethionine levels were also decreased in fasted rats, but S-adenosylhomocysteine levels were increased. Hepatic methionine levels were not changed by food deprivation for 48 hours. On the other hand, hepatic cysteine or taurine levels were increased from $106.2{\pm}4.1$ to $130.0{\pm}2.7$ nmol/g liver or from $2.45{\pm}0.43$ to $5.07{\pm}0.78{\mu}mol/g$ liver, respectively, in 48-hour fasted rats. Activity of cystathionine beta-synthase catalyzed homocysteine to cystathionine, was markedly decreased, but activity of betaine homocysteine methyltransferase was increased in fasted rats, indicating that methylation of homocysteine to methionine is activated. Also activity of cysteine dioxygenase, involved in taurine synthesis, was increased. These results suggested that hepatic methionine levels were maintained in rats fasted for 48 hours through increase in homocysteine methylation, and hepatic GSH may serve as a cysteine supplier reservoir in fasting state.

• Journal of Embryo Transfer
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• v.27 no.4
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• pp.205-209
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• 2012

Transgenic rats and mice are useful experimental animal models for medical research including human disease model studies. Somatic cell nuclear transfer (SCNT) technology is successfully applied in most mammalian species including cattle, sheep, pig and mouse. SCNT is also considered to increase the efficacy of transgenic/knockout mouse and rat production. However, in the area of reproductive biotechnology, the rodent model is inadequate because of technical obstacles in manipulating the oocytes including intracytoplasmic sperm injection and SCNT. In particular, success of rat SCNT is very limited so far. In this review, the history of rodent cloning is described.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.383-387
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• 2006

To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.