COMPARING MUTANTS, SELECTIVE BREEDING, AND TRANSGENICS IN THE DISSECTION OF AGING PROCESSES OF CAENORHABDITIS-ELEGANS

COMPARING MUTANTS, SELECTIVE BREEDING, AND TRANSGENICS IN THE DISSECTION OF AGING PROCESSES OF CAENORHABDITIS-ELEGANS
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DOI:
10.1007/bf01435988
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发表时间:
1993-01-01
期刊:
影响因子:
1.5
通讯作者:
LITHGOW, GJ
LITHGOW, GJ
中科院分区:
生物学4区
文献类型:
--
作者:
JOHNSON, TE;TEDESCO, PM;LITHGOW, GJ

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衰老过程的遗传分析在过去十年中已经成熟,有报道称果蝇和线虫的长寿菌株已经被开发出来。几次鉴定果蝇中具有延长寿命的突变体的尝试都失败了,并分析了这些失败的原因。专性物种(如果蝇)的一个主要问题是近亲繁殖抑制的存在,这使得纯合子的生活史特征分析变得非常困难。然而,几项成功的果蝇衰老遗传分析表明,通过精心设计,对影响寿命的诱导突变进行富有成效的分析是可能的。在秀丽隐杆线虫中,age-1基因的突变导致寿命延长约70%;因此,age-1清楚地说明了生物体衰老的一个过程。该基因位于染色体II上,与原种群中导致大量生育缺陷的基因座(fer15)分离得很好。发育速度或生育能力与与1岁突变相关的寿命之间没有权衡关系。转基因分析证实,生育缺陷可以通过野生型的fer15转化(转基因)来纠正;然而,这些转化的种群的寿命受到转基因阵列以不可预测的方式的影响。age-1基因的分子性质仍然未知,我们将继续努力克隆该基因。
The genetic analysis of aging processes has matured in the last ten years with reports that long-lived strains of both fruit flies and nematodes have been developed. Several attempts to identify mutants in the fruit fly with increased longevity have failed and the reasons for these failures are analyzed. A major problem in obligate sexual species, such as the fruit fly is the presence of inbreeding depression that makes the analysis of life-history traits in homozygotes very difficult. Nevertheless, several successful genetic analyses of aging in Drosophila suggest that with careful design, fruitful analysis of induced mutants affecting life span is possible. In the nematode Caenorhabditis elegans, mutations in the age-1 gene result in a life extension of some 70%; thus age-1 clearly specifies a process involved in organismic senescence. This gene maps to chromosome II, well separated from a locus (fer-15) which is responsible for a large fertility deficit in the original stocks. There is no trade-off between either rate of development or fertility versus life span associated with the age-1 mutation. Transgenic analyses confirm that the fertility deficit can be corrected by a wild-type fer-15 transformant (transgene); however, the life span of these transformed stocks is affected by the transgenic array in an unpredictable fashion. The molecular nature of the age-1 gene remains unknown and we continue in our efforts to clone the gene.