A novel stop codon mutation (X417L) of the ferrochelatase gene in bovine protoporphyria, a natural animal model of the human disease.
A novel stop codon mutation (X417L) of the ferrochelatase gene in bovine protoporphyria, a natural animal model of the human disease.
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牛原卟啉症（人类疾病的自然动物模型）中亚铁螯合酶基因的新终止密码子突变（X417L）。
DOI：
10.1016/s0925-4439(98)00052-0
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Bloomer,JR
中科院分区：
文献类型：
--
作者：
Jenkins,MM;LeBoeuf,RD;Ruth,GR;Bloomer,JR
原卟啉症（PP）是由亚铁螯合酶（FC）活性缺乏引起的，该酶催化血红素生物合成途径的最后一步。牛是除人类以外唯一具有自然发生PP的物种。对于PP表型的表达，在牛中需要两个拷贝的突变基因，而在人中一个拷贝就足够了。我们报告的第一个潜在的致病突变的牛FC基因。对原斑牛和正常牛的肝脏组织进行了FC编码区的测序。在原卟啉FC序列中，在核苷酸位置1250处鉴定到颠换，其将终止密码子改变为亮氨酸（TGA→TTA）。因此，预测突变蛋白质具有额外的27个氨基酸。为了筛选其他牛的G→T颠换，来自临床和生化正常的肝组织的cDNA，以及来自杂合和纯合的受影响动物的cDNA用于等位基因特异性聚合酶链反应。三只正常动物只有G等位基因，五只受影响的动物只有T等位基因，三只杂合子动物同时具有G和T等位基因。这些结果支持我们的假设，这种突变导致PP牛。
Protoporphyria (PP) is caused by a deficiency of ferrochelatase (FC) activity, which catalyzes the final step in the heme biosynthesis pathway. Bovine are the only species other than man with naturally occurring PP. For expression of the PP phenotype, two copies of the mutated gene are necessary in bovine, whereas one copy is sufficient in humans. We report the first potential disease-causing mutation in the bovine FC gene. The coding region of FC was sequenced from the liver tissue of protoporphyric and normal bovine. A transversion was identified at nucleotide position 1250 which changed the stop codon to leucine (TGA→TTA) in the protoporphyric FC sequence. As a consequence, the mutant protein is predicted to have an additional 27 amino acids. To screen other bovine for the G→T transversion, cDNAs from liver tissue of clinically and biochemically normal, and from heterozygous and homozygous affected animals were used for allele-specific polymerase chain reaction. Three normal animals had only the G allele, five affected animals had only the T allele, and three heterozygous animals had both the G and T alleles. These results support our hypothesis that this mutation causes PP in bovine.
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DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bloomer,JR;Hill,HD;Morton,KO;Anderson-Burnham,LA;Straka,JG
通讯作者：
Straka,JG
影响因子：
2.9
作者：
DAILEY, HA;FINNEGAN, MG;JOHNSON, MK
通讯作者：
JOHNSON, MK
编码人亚铁螯合酶的 cDNA 的分子克隆和序列分析。
DOI：
10.1016/s0006-291x(05)80099-3
发表时间：
1990
影响因子：
3.1
作者：
Y. Nakahashi;S. Taketani;M. Okuda;Kyoichi Inoue;Rikio Tokunaga
通讯作者：
Rikio Tokunaga
影响因子：
15.9
作者：
BONKOWSKY, HL;BLOOMER, JR;MAHONEY, MJ
通讯作者：
MAHONEY, MJ
牛原卟啉症：这种遗传性光敏性疾病的第一个非人类模型。
影响因子：
56.9
作者：
G. Ruth;S. Schwartz;B. Stephenson
通讯作者：
B. Stephenson