• BMB Reports
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• 제38권1호
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• pp.89-96
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• 2005

Earlier, we reported that the bacteriophage $\lambda$ P gene product is lethal to Escherichia coli, and the E. coli rpl mutants are resistant to this $\lambda$ P gene-mediated lethality. In this paper, we show that under the $\lambda$ P gene-mediated lethal condition, the host DNA synthesis is inhibited at the initiation step. The rpl8 mutation maps around the 83 min position in the E. coli chromosome and is 94% linked with the dnaA gene. The rpl8 mutant gene has been cloned in a plasmid. This plasmid clone can protect the wild-type E. coli from $\lambda$ P gene-mediated killing and complements E. coli dnaAts46 at $42^{\circ}C$. Also, starting with the wild-type dnaA gene in a plasmid, the rpl-like mutations have been isolated by in vitro mutagenesis. DNA sequencing data show that each of the rpl8, rpl12 and rpl14 mutations has changed a single base in the dnaA gene, which translates into the amino acid changes N313T, Y200N, and S246T respectively within the DnaA protein. These results have led us to conclude that the rpl mutations, which make E. coli resistant to $\lambda$ P gene-mediated host lethality, are located within the DNA initiator gene dnaA of the host.

• Journal of Interdisciplinary Genomics
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• 제3권2호
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• pp.30-34
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• 2021

Campomelic dysplasia (CD) is a rare genetic disorder characterized by multiple skeletal anomalies and the abnormal development of male reproductive organs. To date, the SOX9 gene is the only known causal gene for CD, and approximately 90 causative mutations in SOX9 have been identified worldwide. CD is diagnosed based on clinical characteristics of skeletal dysplasia (e.g., short bowed long bones, kyphoscoliosis, bell-shaped thoracic cage with 11 pairs of ribs, and hypoplastic scapulars), typical facial features of Pierre Robin sequence with cleft palate, and gonadal dysgenesis in 46,XY individuals. Most patients with CD exhibit life-threatening respiratory failure owing to laryngotracheomalacia and hypoplastic thorax during the neonatal period. Although fatal complications decrease after infancy, several medical conditions continue to require proper management. A better understanding of this rare but lethal condition may lead to more appropriate treatments for patients.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2005년도 International Meeting of the Microbiological Society of Korea
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• pp.228.2-228
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• 2005

• 약학회지
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• 제38권3호
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• pp.332-337
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• 1994

Using germinal and somatic cell mutation assaying systems of Drosophila melanogaster, effects of Ginseng and Salvia miltiorrhiza extracts on the in vivo mutagenicity induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) were investigated. For these purpose, the attached-X method and the mwh/flr spot test system which are an X-linked lethal mutation and a somatic chromosome mutation assaying system, respectively, were used. In the induction of X-linked lethal mutations during the spermatogenesis, MNNG showed more actions in the sperm and spermatid stages, in which Ginseng and Salvia miltiorrhiza extracts had remarkable inhibitory effects than other stages. Ginseng and Salvia miltiorrhiza extracts reduced the mutagenicity by MNNG in the mwh/flr system, which reveal that they can inhibit gene mutation, deletion and mitotic chromosomal recombination. These results seem to suggest that Ginseng and Salvia miltiorrhiza extracts may exert their inhibitory effects to in vivo mutagenic and/or carcinogenic properties of DNA-damaging agents.

• Genomics & Informatics
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• 제10권1호
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• pp.16-22
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• 2012

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple fluid-filled cysts that expand over time and destroy renal architecture. The proteins encoded by the $PKD1$ and $PKD2$ genes, mutations in which account for nearly all cases of ADPKD, may help guard against cystogenesis. Previously developed mouse models of $PKD1$ and $PKD2$ demonstrated an embryonic lethal phenotype and massive cyst formation in the kidney, indicating that $PKD1$ and $PKD2$ probably play important roles during normal renal tubular development. However, their precise role in development and the cellular mechanisms of cyst formation induced by $PKD1$ and $PKD2$ mutations are not fully understood. To address this question, we presently created $Pkd2$ knockout and $PKD2$ transgenic mouse embryo fibroblasts. We used a mouse oligonucleotide microarray to identify messenger RNAs whose expression was altered by the overexpression of the $PKD2$ or knockout of the $Pkd2$. The majority of identified mutations was involved in critical biological processes, such as metabolism, transcription, cell adhesion, cell cycle, and signal transduction. Herein, we confirmed differential expressions of several genes including aquaporin-1, according to different $PKD2$ expression levels in ADPKD mouse models, through microarray analysis. These data may be helpful in $PKD2$-related mechanisms of ADPKD pathogenesis.

• 한국환경성돌연변이발암원학회지
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• 제10권2호
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• pp.93-106
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• 1990

The Drosophila temperature-sensitive mutant shibire (shi) is paralyzed at restrictive temperature by a reversible block in synaptic transmission. To explore the functional relationship among shi gene products, viability and temperature-sensitive paralytic behavior were quantitaively analyzed for four shi alleles, shi$^{ts1}$, shi$^{ts2}$, shi$^{ts4}$, and shi$^{ST139}$, and their heteroallelic combinations. The hemizygous combination of shi alleles over deficiency was not completely lethal. shi$^{ts2}$ exhibited distinctively higher viability than other alleles. A novel behavior, bang sensitivity, was also found in shi/Df(1). This bang-sensitive paralytic behavior was compared with that of the typical bang-sensitive mutant flies. Heterozygotes, shi/+, are more severe in temperature sensitivity than deficiency hemizygotes, Df(1)/+. Heteroallelic combinations of shi were less sensitive to high temperature than homozygotes. Among all allelic combinations, shi$^{ts2}$/shi$^{ts4}$ showed an unexpected extreme reduction in temperature sensitivity. The results of allelic interactions among 4 shi alleles suggest that the shi mutations examined behave as antimorphic alleles and that the gene product of shi are likely to function in multimeric forms.

• Clinical and Experimental Pediatrics
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• 제53권12호
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• pp.1022-1025
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• 2010

Thanatophoric dysplasia (TD) is a short-limb neonatal dwarfism syndrome that is usually lethal in the perinatal period. It is characterized by shortening of the limbs, severely small thorax, large head with a prominent forehead, macrocephaly, curved femur, and flattened vertebral bodies. These malformations result from the mutation in fibroblast growth factor receptor 3 (FGFR-3) gene which is located on the short arm of chromosome 4. A definite diagnosis should be established by molecular genetic analysis to find out the abnormal mutations in the $FGFR3$ gene. We confirmed by detection of a R248C mutation in the $FGFR3$ gene in DNA analysis.

• Molecules and Cells
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• 제19권3호
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• pp.452-457
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• 2005

The adaptor protein (AP) complexes are involved in membrane transport of many proteins. There are 3 AP complexes in C. elegans unlike mammals that have four. To study the biological functions of the AP-3 complexes of C. elegans, we sought homologues of the mouse and human genes that encode subunits of the AP-3 complexes by screening C. elegans genomic and EST sequences. We identified single copies of homologues of the ${\mu}3$, ${\sigma}3$, ${\beta}3$ and ${\delta}$ genes. The medium chain of AP-3 is encoded by a single gene in C. elegans but two different genes in mammals. Since there are no known mutations in these genes in C. elegans, we performed RNAi to assess their functions in development. RNAi of each of the genes caused embryonic and larval lethal phenotypes. APM-3 is expressed in most cells, particularly strongly in spermatheca and vulva. We conclude that the products of the C. elegans ${\mu}3$, ${\sigma}3$, ${\beta}3$ and d genes are essential for embryogenesis and larval development.

• 대한화장품학회지
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• 제26권2호
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• pp.41-50
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• 2000

- Biochemical studies show that in the process of mixed melanogenesis, cysteinyldopas are produced first which are next oxidized to give pheomelanin. After all of the cysteine is consumed, eumelanin is then deposited on the preformed pheomelanin. - In vitro and in vivo studies show that tyrosinase activity is the most important factor that regulates the switch of melanogenesis, with higher activities increasing melanogenesis, especially eumelanogenesis. - In culturted melanocytes, the tyrosine to cysteine ratio is critical in determining the eumelanin to pheomelanin ratio. - Our HPLC method to analyze eumelanin and pheomelanin has become a useful tool in the study of melanogenesis regulation. There are many problems to be solved before we fully understand the regulation of melanogenesis. Mutations in mouse models are ideal models for studying the genetic and molecular control of melanogenesis. Even in the mouse models, it is not known how cysteine is excluded from being incorporated into melanins in black and other eumelaninc mice, Conversely, it is not known how cysteine is continuously incorporated into pheomelanin in lethal yellow and recessive yellow mice.

• 생명과학회지
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• 제7권1호
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• pp.49-58
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• 1997

Engralied 5.7kb upstream sequence와 E. colilacZ의 융합 유전자를 가진 P[en-lacZ] 인자를 jumpstart 기법을 이용하여, ryXho25 strain의 초파리 48A 염색체 위치로부터 새로운 위치로 삽입하였다. 총 3315의 유전적 교배를 통해서, P[en-lacZ] 가 다른 염색체 상으로 삽인된 113 계통을 얻었다. X-gal 염색으로 이들 113 계통의 3령기 유충 조직에서의 $\beta$-galactosidase 발현을 조사하였다. 도한 113 계통 중 7계통이 열성치사돌연변이인 것으로 동정되었다. 이들 7 계통 중 초기 배발생 과정에서 치사하는 것으로 조사된 #1119의 초기 배발생 과정에서의 ${\beta}$-galactosidase 발현과 핵의 이동 및 세포화 양상을 조사하였다. 본 연구에서 얻어진 P[en-lacZ] 삽입 돌연변이체들은 앞으로 Drosophila 발생에 관련된 유전자들의 구조와 기능을 연구하는데 활용될 수 있을 것이다.