MOLECULAR GENETICS OF HEME BIOSYNTHETIC ENZYMES
MOLECULAR GENETICS OF HEME BIOSYNTHETIC ENZYMES
批准号:
3237194
负责人:
SAMUEL H BOYER
金额:
$19.5万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1987
资助国家:
美国
项目状态:
已结题
起止时间:
1987-01-01 至 1991-12-31
关键词:
5 aminolevulinate synthase biological polymorphism complementary DNA enzyme induction /repression enzyme structure erythroleukemia erythropoiesis gene dosage gene expression heme human subject molecular cloning monoclonal antibody mutant nucleic acid sequence population genetics porphobilinogen synthase porphyrin biosynthesis
中文摘要
关于血红素代谢及其扰动,我们知道得很多,
这一重要物质的产生的分子机制
材料是规范的。 我们的目标是描绘这样的机制,
关于血红素生物合成中前两种酶的表达,
途径:δ-氨基乙酰丙酸合成酶(ALAS)和δ-氨基乙酰丙酸
酶(ALAD)。 为了这项事业,我们带来了经过验证的老鼠肝脏
ALAD-cDNA克隆及抗大鼠肝ALAD单克隆抗体的研制
和阿拉斯。 设定了七个具体目标:第一,隔离,
全长小鼠和大鼠ALAD-cDNA的表征;第二,分离
以及两个物种中ALAD基因组序列的描绘;第三,
证实了我们的发现,ALAD基因剂量的差异帐户
对于近交系小鼠之间ALAD酶活性的增量差异,
第四,评估(a)ALAD基因拷贝的遗传多态性
异交小鼠和野生小鼠中的数量,以及(B)其与
环境铅;第五,ALAD的分子性质的描绘,
非典型的设置,例如,红白血病K562细胞,胎儿
第六,分离全长ALAS-cDNA,
从大鼠和小鼠肝脏中提取相应的基因DNA;第七、应用
ALAS-和ALAD-探针的分子机制解剖
在鼠红白血病细胞中酶表达的快速流动的基础,
在小鼠红系祖细胞中,以及在用
卟啉生成剂。
英文摘要
Much is known about heme metabolism and its perturbations, little is known
of the molecular mechanisms by which the production of this essential
material is regulated. Our goals are to delineate such mechanisms with
respect to the expression of the first two enzymes in the heme biosynthetic
pathway: delta-aminolevulinate synthase (ALAS) and delta-aminolevulinate
dehydrase (ALAD). To this undertaking, we bring verified rat liver
ALAD-cDNA clones and monoclonal antibodies developed against rat liver ALAD
and ALAS. Seven specific aims are set: first, isolation and
characterization of full-length mouse and rat ALAD-cDNA; second, isolation
and delineation of ALAD genomic sequences in both species; third,
verification of our finding that differences in ALAD-gene dosage account
for incremental differences in ALAD enzymatic activity between inbred mouse
strains; fourth, assessment of (a) genetic polymorphism for ALAD-gene copy
number in outcrossed and feral mice and (b) its possible relationship to
environmental lead; fifth, delineation of the molecular nature of ALAD in
settings where it is atypical, e.g., erythroleukemia K562 cells, fetal
liver and human mutants; sixth, isolation of full-length ALAS-cDNA and
corresponding gene DNA from rat and mouse liver; and seventh, application
of ALAS- and ALAD-probes to the dissection of molecular mechanisms
underlying rapid flux of enzyme expression in murine erythroleukemia cells,
in murine erythroid progenitors, and in the livers of animals treated with
porphyrinogenic agents.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
GENE EXPRESSION DURING ERYTHROID MATURATION
-
批准号:3237193
-
项目类别:
-
资助金额:$23.48万
-
财政年份:1988
-
负责人:SAMUEL H BOYER
-
依托单位:
GENE EXPRESSION DURING ERYTHROID MATURATION
-
批准号:3237191
-
项目类别:
-
资助金额:$21.44万
-
财政年份:1988
-
负责人:SAMUEL H BOYER
-
依托单位:
GENE EXPRESSION DURING ERYTHROID MATURATION
-
批准号:3237192
-
项目类别:
-
资助金额:$22.76万
-
财政年份:1988
-
负责人:SAMUEL H BOYER
-
依托单位:
MOLECULAR GENETICS OF HEME BIOSYNTHETIC ENZYMES
-
批准号:3237199
-
项目类别:
-
资助金额:$20.29万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MOLECULAR GENETICS OF HEME BIOSYNTHETIC ENZYMES
-
批准号:3237198
-
项目类别:
-
资助金额:$19.21万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MURINE ERYTHROPOIETIN--RESPONSE AND RECEPTORS
-
批准号:3239911
-
项目类别:
-
资助金额:$29.54万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MURINE ERYTHROPOIETIN--RESPONSE AND RECEPTORS
-
批准号:3239912
-
项目类别:
-
资助金额:$28.24万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MURINE ERYTHROPOIETIN--RESPONSE AND RECEPTORS
-
批准号:3239910
-
项目类别:
-
资助金额:$30.4万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MECHANISMS OF MURINE CFU-E MATURATION
-
批准号:2141104
-
项目类别:
-
资助金额:$18.13万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MURINE ERYTHROPOIETIN--RESPONSE AND RECEPTORS
-
批准号:3239909
-
项目类别:
-
资助金额:$29.42万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MURINE ERYTHROPOIETIN--RESPONSE AND RECEPTORS
-
批准号:3239907
-
项目类别:
-
资助金额:$28.85万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MOLECULAR GENETICS OF HEME BIOSYNTHETIC ENZYMES
-
批准号:3237200
-
项目类别:
-
资助金额:$21.0万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
MOLECULAR GENETICS OF HEME BIOSYNTHETIC ENZYMES
-
批准号:3237201
-
项目类别:
-
资助金额:$20.39万
-
财政年份:1987
-
负责人:SAMUEL H BOYER
-
依托单位:
海外基金