• Title/Summary/Keyword: MC1R

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Development of Melanotropin Antagonists: Investigating Potent and Specific Ligands for New Receptors

  • Lim, Sejin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.11a
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    • pp.153-159
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    • 1996
  • ${\alpha}$-Melanotropin (Ac-Ser-Tyr- Ser-Met-Glu$\^$5/-His-Phe-Arg-Trp-Gly$\^$10/-Lys-Pro-Val-NH$_2$) is one of the first peptide hormones to be isolated and have its structure determined. It was early recognized to have essentially the same N-terminal tridecapeptide sequence as adrenocorticotropic hormone (ACTH) except that the N-terminal was acetylated in the case of ${\alpha}$-MSH but not in the case of ACTH, indicating that their biosyntheses were different (Figure 1). Subsequently it was discovered that ${\alpha}$-MSH and ACTH were derived from the same gene, currently referred to as proopiomelanocortin (POMC). Its original bioactivity was pigmentation, but it also was recognized that it may have activity in the central nervous system, though the precise nature of these central activities have been controversial. The recent cloning and expression of five melanocortin receptors, with the MC3 and MC4 receptors found primarily in the brain and the MC5 receptor (MC5-R) found throughout the body, has provided new impetus to understand the structure-activity relationships of ${\alpha}$-MSH at these receptors. The effects of ${\alpha}$-MSH on pigmentation are mediated by the MC1-R expressed specifically on the surface of melanocytes. Similarly the MC2-R is involved in the regulation of adrenal steroidogenesis by ACTH. However, given the complexity of expression of the MC3, MC4, and MC5 receptors, it has not been possible to identify any simple correlations between these receptors and the reported biological activities of the melanocortin peptides. Consequently, potent and receptor specific agonists and especially antagonists would be extremely valuable tools for the determination of the physiological roles of the MC3, MC4, and MC5 receptors. Though the extensive structure-activity relationships have provided much information on agonist activity related to pigmentary effects, only recently has it been possible to begin to systematically develop potent and selective antagonists.

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Investigation of MC1R SNPs and Their Relationships with Plumage Colors in Korean Native Chicken

  • Hoque, M.R.;Jin, S.;Heo, K.N.;Kang, B.S.;Jo, C.;Lee, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.5
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    • pp.625-629
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    • 2013
  • The melanocortin 1 receptor (MC1R) gene is related to the plumage color variations in chicken. Initially, the MC1R gene from 30 individuals was sequenced and nine polymorphisms were obtained. Of these, three and six single nucleotide polymorphisms (SNPs) were confirmed as synonymous and nonsynonymous mutations, respectively. Among these, three selected SNPs were genotyped using the restriction fragment length polymorphism (RFLP) method in 150 individuals from five chicken breeds, which identified the plumage color responding alleles. The neighbor-joining phylogenetic tree using MC1R gene sequences indicated three well-differentiated different plumage pigmentations (eumelanin, pheomelanin and albino). Also, the genotype analyses indicated that the TT, AA and GG genotypes corresponded to the eumelanin, pheomelanin and albino plumage pigmentations at nucleotide positions 69, 376 and 427, respectively. In contrast, high allele frequencies with T, A and G alleles corresponded to black, red/yellow and white plumage color in 69, 376 and 427 nucleotide positions, respectively. Also, amino acids changes at position Asn23Asn, Val126Ile and Thr143Ala were observed in melanin synthesis with identified possible alleles, respectively. In addition, high haplotype frequencies in TGA, CGG and CAA haplotypes were well discriminated based on the plumage pigmentation in chicken breeds. The results obtained in this study can be used for designing proper breeding and conservation strategies for the Korean native chicken breeds, as well as for the developing breed identification markers in chicken.

Coat colour phenotype of Qingyu pig is associated with polymorphisms of melanocortin receptor 1 gene

  • Wu, Xiaoqian;Tan, Zhendong;Shen, Linyuan;Yang, Qiong;Cheng, Xiao;Liao, Kun;Bai, Lin;Shuai, Surong;Li, Mingzhou;Li, Xuewei;Zhang, Shunhua;Zhu, Li
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.7
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    • pp.938-943
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    • 2017
  • Objective: Qingyu pig, a Chinese indigenous pig breed, exhibits two types of coat colour phenotypes, including pure black and white with black spotting respectively. Melanocortin receptor 1 (MC1R) and agouti signaling protein (ASIP) are two widely reported pivotal genes that significantly affect the regulation of coat colour. The objectives of this study were to investigate whether the polymorphisms of these two genes are associated with coat colour and analyze the molecular mechanism of the coat colour separation in Qingyu pig. Methods: We studied the phenotype segregation and used polymerase chain reaction amplification and Sanger sequencing to investigate the polymorphism of MC1R and ASIP in 121 Qingyu pigs, consisting of 115 black and 6 white with black spotted pigs. Results: Coat colour of Qingyu pig is associated with the polymorphisms of MC1R but not ASIP. We only found 2 haplotypes, $E^{QY}$ and $E^{qy}$, based on the 13 observed mutations from MC1R gene. Among which, $E^{qy}$ presented a recessive inheritance mode in black spotted Qingyu pigs. Further analysis revealed a g.462-463CC insertion that caused a frameshift mutation and a premature stop codon, thus changed the first transmembrane domain completely and lost the remaining six transmembrane domains. Altogether, our results strongly support that the variety of Qingyu pig's coat colour is related to MC1R. Conclusion: Our findings indicated that black coat colour in Qingyu pig was dominant to white with black spotted phenotype and MC1R gene polymorphism was associated with coat colour separation in Qingyu pig.

Investigation of Coat Color Candidate Genes in Korean Cattle(Hanwoo) (한우에서 모색관련 유전자 변이에 관한 연구)

  • Do, K.T.;Shin, H.Y.;Lee, J.H.;Kim, N.S.;Park, E.W.;Yoon, D.H.;Kim, K.S.
    • Journal of Animal Science and Technology
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    • v.49 no.6
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    • pp.711-718
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    • 2007
  • Most cattle breeds have a coat color pattern that is characteristic for the breed. Korean cattle(Hanwoo) has a coat color ranging from yellowish brown to dark brown including a red coat color. Variation in the Hanwoo coat color is likely to be the effects of modified genes segregating within the Hanwoo breed. MC1R encoded by the Extension(E) locus was almost fixed with recessive red e allele in the Hanwoo, but other gene(s) might be affecting the variation of the Hanwoo coat color into yellowish to red brown. We have analyzed a segregation of coat color in the F2 families generated from two Hanwoo bulls(yellowish brown) mated to six F1 dams(black) derived from Hanwoo and Holstein crosses. Segregation of coat color in the offspring found a ratio of 1(yellowish brown) : 1(black) and this ratio indicates that a single gene may play a major role for the Hanwoo coat color. We further investigated SNPs in MC1R, ASIP and TYRP1 loci to determine genetic cause of the Hanwoo coat color. Several polymorphisms within ASIP intron 2 and TYRP1 exons were found but not conserved within the Hanwoo population. However, the segregation of the MC1R e allele was completely associated with the Hanwoo coat color. Based on this information, it is clear that the MC1R e allele is mainly responsible for the yellowish red Hanwoo coat color. Further study is warrant to identify possible genetic interaction between MC1R e allele and other coat color related gene(s) for the variation of Hanwoo coat color from yellowish brown to dark brown. (Key words : Hanwoo, Coat color, SNP, MC1R, ASIP, TYRP1)

Relation of Expression Levels of Melanin Synthesis Genes according to the MC1R Genotypes with the Coat Color Patterns in Hanwoo, Jeju Black Cattle and Holstein (한우와 제주흑우, 홀스타인에서 MC1R 유전자형에 따른 melanin 생합성 유전자들의 발현수준과 모색 출현양상의 관계)

  • Lee, Sung-Soo;Yang, Young-Hoon;Cho, In-Cheol;Kim, Nam-Young;Ko, Moon-Suck;Jung, Ha-Yeon;Han, Sang-Hyun
    • Journal of Life Science
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    • v.19 no.3
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    • pp.384-389
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    • 2009
  • This study was carried out to elucidate the relation between expression levels of three melanin synthesis genes (Tyrosinase, Tyrosinase-related protein 1 and Dopachrome tautomerase) according to the Melanocortin-1 receptor genotypes with coat color patterns in Hanwoo cattle, Jeju black cattle and Holsteins. Using real-time semiquantitative reverse transcription-PCR assay (RT-PCR), the expression levels of these three genes were analyzed in skin tissues from four representative coat colored areas: yellowish-brown from MC1R e/e Hanwoo, wild type black from $E^+/E^+$ Jeju black cattle (JBC), and dominant black and white pied regions from $E^D/E^D$ Holstein. The TYR, TYRP1 and DCT genes showed higher expression levels of 4.5, 2.3 and 2.5 times higher in the black skin area of Holsteins than those of from JBC, respectively (p<0.001). In addition, the expression levels of these three genes from JBC were significantly higher than those from Hanwoo cattle (p<0.001). These results show that coat color phenotypes in Hanwoo cattle, JBC and Holsteins is directly correlated with TRY, TYRP1 and DCT transcription levels, which probably reflected involvement with MC1R genotypes; e/e in Hanwoo, $E^+/E^+$ in JBC and $E^D/E^D$ in Holsteins. Consequently, this study suggested that the status of MC1R protein may not only induce the transcription activities of a series of TYR and its related genes responsible for melanin synthesis, but also determine the levels of total melanin contents in bovine skin.

MC1R Genotypes, Coat Color, and Muzzle Phenotype Variation in Korean Native Brindle Cattle (MC1R 유전자의 유전자형과 칡소의 모색 발현 및 비경색 분포에 관한 연구)

  • Park, Jae-Hee;Lee, Hae-Lee;Kim, Yong-Su;Kim, Jong-Gug
    • Journal of Animal Science and Technology
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    • v.54 no.4
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    • pp.255-265
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    • 2012
  • The objectives of this study were to investigate MC1R genotype, coat color, and muzzle phenotype variationsin the Korean native brindle cattle (KNBC) maintaining family lines and to establish the mating system for increased brindle coat color appearance. KNBC with genotype and phenotype records were selected as experimental animals. The relationship between melanocortin 1 receptor (MC1R) genotypes, verified by PCR-RFLP, and brindle coat color appearance was determined. Fragments of the MC1R gene amplified by PCR were digested with MspI and RFLP was determined. KNBC had $E^+E^+$, $E^+e$, and ee genotypes. The $E^+e$ genotype was most common with 65%, compared to $E^+E^+$ (33.33%), or ee (1.67%). When the sire had $E^+e$ genotype and the dam had $E^+E^+$ genotype, and both of them had the whole body-brindle coat color, all of their offspring (4/4) had whole body-brindle coat color. When the sire had $E^+E^+$ genotype and the dam had $E^+e$ genotype, and both had whole body-brindle coat color, 44.44% (4/9) of the offspring had whole body-brindle coat color. The mating between the sires and dams with these two genotypes with whole body-brindle coat color may have the highest whole body-brindle coat color appearance in their offspring. Muzzle grades 3 or 4 were more common than other muzzle grades. This is the first report indicating the segregation of MC1R genotypes and the inheritance of coat color through family lines in KNBC. The mating system proposed from this study may increase the possibility of brindle coat color appearance in KNBC.

Protective Effect of PineXol® on Hydrogen Peroxide-induced Apoptosis on SK-N-MC Cells and Focal Ischemia Rodent Models (파인엑솔이 과산화수소로 유도된 SK-N-MC 세포와 뇌졸중 백서 모델에서의 보호효과)

  • Hong, Soon-O;Han, Kyung-Hoon;Lee, Seung-Hee;Kim, Doh-Hee;Song, Kwan-Young;Han, Sung-Hee
    • The Korean Journal of Food And Nutrition
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    • v.29 no.6
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    • pp.923-929
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    • 2016
  • The purpose of this study was to evaluate the protective effect of $PineXol^{(R)}$ on $H_2O_2$-induced cell death in SK-N-MC cells, and in early stage focal ischemia rodent model. SK-N-MC cells were pre-treated with $200{\mu}M$ $H_2O_2$ or various concentrations of $PineXol^{(R)}$ (10, 30, and 50 pg/mL) for 24 h, and then exposed to $H_2O_2$ for 3 h. Cell death was assessed by the CCK-8 assay, reactive oxygen species (ROS) assay, and lactate and dehydrogenase (LDH) release assay. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) expressions were also analyzed by western blotting. Focal ischemia rodent model was used as the in vivo model, and different concentrations of $PineXol^{(R)}$ (1, 10, and 100 mg/kg) were administered. One week after administration, reduction of infarct volume was analyzed by TTC staining. Cell viability of $H_2O_2$-treated SK-N-MC cells significantly increased by pre-treatment of $PineXol^{(R)}$ (p<0.05). $PineXol^{(R)}$ pre-treatment also induced significant decrease of ROS and LDH expressions. However, $PineXol^{(R)}$ did not affect the infarct volume. These results suggest that $PineXol^{(R)}$ has significant neuroprotective effect in vitro, but statistical significance was not confirmed in the in vivo focal ischemia model.

Development of molecular markers among Barred Plymouth rock, Korean Ogol Chicken and White Leghorn

  • Choi, Jin-Won;Lee, Eun-Young;Lee, Jae-Hee;Kim, Duk-Kyung;Kim, Hee-Bal;Han, Jae-Yong
    • Proceedings of the Korea Society of Poultry Science Conference
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    • 2005.11a
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    • pp.68-69
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    • 2005
  • To identify germline chimeric chicken using germ cell transplantation method, the testcross, spends much time, labor and cost to perform, is the only way for distinguishing germline chimeric chicken from normal one And to enhance the method, development of breed-specific molecular markers have been needed. We have just identified breed-specific sequence polymorphisms among Barred Plymouth rock, Korean Ogol Chicken and White Leghorn in PMEL17 and MC1R gene the loci of which are identical to dominant white and extended black loci. These sequence polymorphism will be very useful for screening germline chimera.

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Investigation of TYR and MC1R polymorphisms in Korean native chickens and the commercial chickens (토종닭과 실용계에서 TYR 및 MC1R 유전자의 변이 분석)

  • Heo, Kang-Nyeong;Choo, Hyo-Jun;Seo, Bo-Young;Park, Mi-Na;Jung, Kie-Chul;Hwang, Bo-Jong;Kim, Hak-Kyu;Hong, Eui-Chul;Seo, Ok-Suk;Kang, Bo-Seok
    • Korean Journal of Agricultural Science
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    • v.38 no.3
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    • pp.465-471
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    • 2011
  • The commercial Korean native chickens (WR_CC) was developed by crossing a few native chicken breeds in Korea. In order to investigate the breed identification markers, SNPs from TYR gene and MC1R gene, which are associated with skin and feather colors respectively, were initially identified. In case of 3 identified SNPs in the TYR gene, yellow shank color was identified in Loss, Harvard, AA, RIR and CC, which have the fixed SNPs in most of the animals. On the other hand, SNP variations were observed in KNC_RB, C_B, WR_CC and HH_CC, which have the black, yellow and mixed color with black and yellow shank colors. Also, the investigation of 3 SNPs in the MC1R gene indicated that there were associations between shank and feather colors in RIR, SF, KNC_B, C_B and RIR. However, these results are not consistent among breeds. These SNP type inconsistencies within breeds suggested that the selection was performed based on the phenotypes, which is not include the genotype information. Thus, selection based on genetic information is required in the future.

Highly Manufacturable 65nm McFET (Multi-channel Field Effect Transistor) SRAM Cell with Extremely High Performance

  • Kim, Sung-Min;Yoon, Eun-Jung;Kim, Min-Sang;Li, Ming;Oh, Chang-Woo;Lee, Sung-Young;Yeo, Kyoung-Hwan;Kim, Sung-Hwan;Choe, Dong-Uk;Suk, Sung-Dae;Kim, Dong-Won;Park, Dong-Gun
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.6 no.1
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    • pp.22-29
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    • 2006
  • We demonstrate highly manufacturable Multi-channel Field Effect Transistor (McFET) on bulk Si wafer. McFET shows excellent transistor characteristics, such as $5{\sim}6 times higher drive current than planar MOSFET, ideal subthreshold swing, low drain induced barrier lowering (DIBL) without pocket implantation and negligible body bias dependency, maintaining the same source/drain resistance as that of a planar transistor due to the unique feature of McFET. And suitable threshold voltage ($V_T$) for SRAM operation and high static noise margin (SNM) are achieved by using TiN metal gate electrode.