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      • KCI등재

        Change in the Gastro-Intestinal Tract by Overexpressed Activin Beta A

        김미녀,김영일,조정희,Kelly E Mayo,조병남 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.12

        Originally, activins were identified as stimulators of FSH release in reproduction. Other activities, including secondary axis formation in development, have since been revealed. Here, we investigated the influence of activin βA on the body, including the gastro-intestinal (GI) tract. Initially, the activin βA protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin βA in muscle was higher in female than male mice. Subsequent results revealed that stomach and intestine were severely damaged in pCMVrAct- injected mice. At the cellular level, loss of parietal cells was observed, resulting in increased pH within the stomach. This phenomenon was more severe in male than female mice. Consistent with damage of the stomach and intestine, activin βA often led to necrosis in the tip of the tail or foot, and loss of body weight was observed in pCMVrAct- injected male but not female mice. Finally, in pCMVrAct- injected mice, circulating activin βA led to death at supraphysiological doses, and this was dependent on the strain of mice used. Taken together, these results indicate that activin βA has an important role outside of reproduction and development, specifically in digestion. These data also indicate that activin βA must be controlled within a narrow range because of latent lethal activity. In addition, our approach can be used effectively for functional analysis of secreted proteins.

      • KCI등재

        Urine Analysis in Transgenic Mice Expressing the Growth Hormone-releasing Factor

        Cho Byung-Nam,Jung Hoi-Kyung,Yoon Yong-Dal,Mayo Kelly-E 한국발생생물학회 2002 발생과 생식 Vol.6 No.1

        생쥐에서 페르몬으로 알려진 소수성의 분자와 결합하는 major urinary proteins(MUPs)는 부분적으로 성장 호르몬(GH)의 조절을 받는다. 본 연구에서는 MT-GRF로 형질전환되어 성장호르몬이 증가된 생쥐에서 MUP의 발현을 조사하였다. 이 MT-GRF로 형질전환된 생쥐의 소변에서 MUP이 대조군보다 심하게 저하되어 나타났고, 암컷보다 수컷에서 더 저하되어 나타났다. 또한 MT-GRF를 근육에 주사한 생쥐에서도 MUP는 저하되어 나타났다. The major urinary proteins(MUPs) of mice that bind hydrophobic molecules known as pheromones are regulated in part by the actions of growth hormone. The expression of the MUPs was therefore investigated in transgenic mice that express a human growth hormone-releasing factor gene from a metallothionein gene promoter(MT-GRF) and as a result have elevated growth hormone levels. MUPs were severely down-regulated in the urine of these animals compared to normal mice or to control transgenic mice expressing another gene(the inhibin a subunit) from the same metallothionein promoter(MT-Inh) and more MUPs disappeared in male mice than female ones. MUPs were also down-regulated in the urine of the UT-GRF-injected mice. In addition, it was observed that the urine of the MT-GRF mice included a high molecular weight protein that co-migrates with the major serum protein albumin, indicating an impairment in glomerular filtration within the kidney. The urinary loss of serum proteins was more severe in male MT-GRF mice than female ones. Thus the overexpression of human GRF mimics changes observed in MUP protein expression and glomerular function in other models of growth hormone hypersecretion with sex-dependent differential effects.

      • KCI등재

        Change in the Gastro-Intestinal Tract by Overexpressed Activin Beta A

        Kim, Mi-Nyeu,Kim, Young Il,Cho, Chunghee,Mayo, Kelly E.,Cho, Byung-Nam Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.12

        Originally, activins were identified as stimulators of FSH release in reproduction. Other activities, including secondary axis formation in development, have since been revealed. Here, we investigated the influence of activin ${\beta}_A$ on the body, including the gastro-intestinal (GI) tract. Initially, the activin ${\beta}_A$ protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin ${\beta}_A$ in muscle was higher in female than male mice. Subsequent results revealed that stomach and intestine were severely damaged in pCMV-rAct-injected mice. At the cellular level, loss of parietal cells was observed, resulting in increased pH within the stomach. This phenomenon was more severe in male than female mice. Consistent with damage of the stomach and intestine, activin ${\beta}_A$ often led to necrosis in the tip of the tail or foot, and loss of body weight was observed in pCMV-rAct-injected male but not female mice. Finally, in pCMV-rAct-injected mice, circulating activin ${\beta}_A$ led to death at supraphysiological doses, and this was dependent on the strain of mice used. Taken together, these results indicate that activin ${\beta}_A$ has an important role outside of reproduction and development, specifically in digestion. These data also indicate that activin ${\beta}_A$ must be controlled within a narrow range because of latent lethal activity. In addition, our approach can be used effectively for functional analysis of secreted proteins.

      • KCI등재

        Changes in the Reproductive Functions of Mice due to Injection of a Plasmid Expressing an Inhibin a-Subunit into Muscle: a Transient Transgenic Model

        Byung-Nam Cho,Jung Mi Ahn,Hoi Kyung Jung,Chunghee Cho,최돈찬,Kelly E Mayo 한국분자세포생물학회 2004 Molecules and cells Vol.18 No.1

        Inhibin is a gonadal hormone composed of an α- subunit and one of two β-subunits (βA, βB), and its primary role is to inhibit FSH secretion by the pituitary. To investigate the roles of inhibin α in the reproductive system, an expression plasmid, pCMV-rINA, with the rat inhibin α cDNA fused to the cytomegalovirus promoter, was introduced into muscle by direct injection. Inhibin α mRNA was detected in the muscle by RT-PCR and Southern blot analysis. Inhibin protein was also detected, and Western blot analysis revealed a relatively high level of serum inhibin, but not of activin βA. The estrous cycle of the pCMVrINA- injected mice was extended, but there was no change in levels of pituitary FSH mRNA or serum FSH and no ovarian cysts were observed. When injected female mice were mated with males of proven fertility, litter size increased. Surprisingly, the embryos of pregnant females injected with pCMV-rINA, were retarded in growth and had defects in internal organs. When male mice were injected, testicle weight increased slightly without any noticeable change in the histology of the seminiferous tubules. Taken together, our data indicate that the inhibin α subunit influences a number of the reproductive functions of female mice.

      • KCI등재

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