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Human 성장호르몬을 도입한 Transgenic Rats의 작출과 번식표현형에 관한 연구 II. 형질전환된 Rats의 hGH수준이 번식표현형에 미치는 영향
장규태,김성현,성환후,주학진,박미령,윤창현 한국동물번식학회 1998 Reproductive & developmental biology Vol.22 No.2
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.
장규태,김성현,성환후,주학진,박미령,윤창현 한국동물번식학회 1998 Reproductive & developmental biology Vol.22 No.2
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.
Ji Soon Sin,Su Youn Yim,Yeon Kyung Lee,Chul Kyu Kim,Byung Guk Kim,Sun Bo Shim,Seung Wan Jee,Su Hae Lee,Chang Jun Bae,Jong-Min Woo,Sang Seop Kim,Mi Kyong Jang,Jung Sik Cho,Sung Man Kim,Chung Yeol Lee,K 한국실험동물학회 2008 Laboratory Animal Research Vol.24 No.3
Selenium and selenoprotein are tightly associated with the protective and antioxidant effects against damage induced by various metal ions in the kidney. Many effects of these kidney damage and stress are mediated by the mitogen-activated protein kinase signaling pathways. To investigate whether selenium treatment and selenoprotein M overexpression would impact on the mitogen-activated protein kinase pathway in the kidney, we detected the phosphorylation level of major components involving p38 kinase, c-jun N-terminal kinase and extracellular signaling-regulated kinase in the transgenic rat overexpressing human selenoprotein M gene. At first, western blot analysis showed that transgenic rats used in this study had the highly expression level of selenoprotein M in the kidney tissue, respectively. The phosphorylation level of p38 kinase was slightly increased in the wild-type rats of selenium-treated group, while did not change in the transgenic rats. Also, the phosphorylation level of c-jun N-terminal kinase was very similar with the change patterns of p38 kinase. Especially, extracellular signaling-regulated kinase was significantly inhibited in the selenium-treatment group. Furthermore, this inhibition rate of extracellular signaling-regulated kinase was stimulated by selenium M overexpression in the transgenic rats. These results suggest that the overexpression of selenoprotein M could effectively influenced the kidney cell proliferation, differentiation and apoptosis through the inhibition of extracellular signaling-regulated kinase in the kidney tissue of transgenic rat.
Dae Youn Hwang,Ji Soon Sin,Yong Kyu Kim,Chuel Kyu Kim,Byung Guk Kim,Sun Bo Shim,Seung Wan Jee,Su Hae Lee,Chang Jun Bae,Byoung Chun Lee,Mee Kyung Jang,Min Sun Kim,Su Youn Yim,Jung Sik Cho,Kab Ryong Cha 한국실험동물학회 2007 Laboratory Animal Research Vol.23 No.3
Selenoprotein M (SeIM) is a eukaryotic selenoprotein containing one selenocysteine (Sec) and Sec insertion sequence (SECIS) in 3' untranslated regions. In order to examine whether SelM expression and selenium treatment were influenced on expression level of the apoptosis-related proteins, pCMV/hlDE fusion gene were overexpressed in the HEK 293 cell line and hSelM-Tg rat. Herein, it is concluded that; ⅰ) two transgenic mice were identified by PCR analysis using specific primers by screening 28 newborn founder mice, ⅱ) the GFP-hSeIM fusion protein were successfully detected on the protein level in the HEK 293 cell line and hSeIM-Tg rat. ⅲ) it was also observed that p53 proteins were significantly changed in the HEK 293 cell under the condition of hSeIM overexpression and selenuim treatment, while not changed in the kidney tissue of hSeIM-Tg rat. ⅳ) Bax proteins were significantly changed in the kidney of hSeIM-Tg rat under the condition of hSeIM overexpression and sel treatment, while not changed in the HEK 293 cell line. ⅴ) Bel2 proteins in the HEK 293 cell were significantly decreased in the hSeIM transfectants, but hSeIM-Tg rat were shown the different expression patterns in the sel treated condition. These results suggest that selenium treatment and SeIM overexpression were differently influenced the expressions of apoptosis-related proteins in the tumor cell line and transgenic tissue
Kim, You-Sun,Son, Mi-Won,Ko, Jun-Il,Cho, Hyeon,Yoo, Moo-Hi,Kim, Won-Bae,Song, In-Sung,Kim, Chung-Yong The Pharmaceutical Society of Korea 1999 Archives of Pharmacal Research Vol.22 No.4
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.
Yoen Kyung Lee,Su Youn Yim,Seung Eun Jung,Ji Ha Kim,Ji Eun Kim,Eon Pil Lee,Hae Wook Choi,Hong Sung Kim,Jae Ho Lee,Young Jin Jung,Jung Sik Cho,Chung-Yeol Lee,Hong Joo Son,Dae Youn Hwang 한국실험동물학회 2009 Laboratory Animal Research Vol.25 No.3
Selenium (Sel) is widely distributed through the body, and performs a crucial role in the regulation of organ function. In this study, in order to determine whether Sel treatment and selenoprotein M (SelM) overexpression could affect the extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinase (MAPK) pathway, the level of ERK phosphorylation was assessed in various tissues of CMV/ EGFP-hSelM Tg rats after Sel treatment. Herein, our results demonstrated that SelM overexpression induces a slight increase in the ERK MAPK pathway in the heart, liver, and intestine, while no changes were detected in the brain, lung, and kidney. After Sel treatment, the liver and intestine evidenced higher levels of ERK activation than were induced by SelM overexpression. In particular, costimulation with SelM overexpression and Sel treatment induced a dramatic increase in the phosphorylation of ERK in the brain, heart, liver, and intestine, while a reduction in ERK phosphorylation was noted in the kidneys. The results of this study suggest that Sel and SelM may contribute to the regulation of a variety of functions via the induction of ERK phosphorylation in different organs of CMV/EGFP-hSelM Tg rats.
Genetic Quality Control of the Rat Strains at the National Bio Resource Project-Rat
Kuramoto, Takashi,Nakanishi, Satoshi,Yamasaki, Ken-ichi,Kumafuji, Kenta,Sakakibara, Yuichi,Neoda, Yuki,Takizawa, Akiko,Kaneko, Takehito,Otsuki, Mito,Hashimoto, Ryoko,Voigt, Birger,Mashimo, Tomoji,Seri Korean Society for Bioinformatics 2010 Interdisciplinary Bio Central (IBC) Vol.2 No.4
The National Bio Resource Project-Rat (NBRP-Rat) comprises the largest bank of laboratory rat (Rattus norvegicus) strains in the world. Its main focus is to develop infrastructure that will facilitate the systematic collection, preservation, and provision of rat strains. To breed effectively more than 180 rat strains in living stock, we establish the genetic control system in which a systematic set of genetic diagnoses and genetic monitoring are included. Genetic monitoring is performed by using 20 polymorphic markers. Monitoring is carried out when a living animal stock is re-established by using cryopreserved embryos or sperm or when a rat strain is first introduced to the NBRP-Rat by a depositor. Additional monitoring is then carried out on each strain every two years. Genetic diagnosis is performed largely by employing the Amp-FTA method. Protocols which detail how to perform a genetic diagnosis of 11 transgenes and 24 mutations have been made. Among the mutations, nine can be detected by simple gel electrophoresis of the PCR products, 11 by restriction enzyme treatment of the PCR products, and four by direct PCR product sequencing. Using this genetic control system, the NBRP-Rat can guarantee the genetic quality of its rat strains.