GENETIC-MAPPING OF THE ATHYMIC NUDE (RNU) LOCUS IN THE RAT TO A REGION CHROMOSOME-10

GENETIC-MAPPING OF THE ATHYMIC NUDE (RNU) LOCUS IN THE RAT TO A REGION CHROMOSOME-10
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DOI:
10.1007/bf00364661
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发表时间:
1993-01-01
期刊:
影响因子:
2.5
通讯作者:
WILDER, RL
WILDER, RL
中科院分区:
生物学4区
文献类型:
--
作者:
CASH, JM;REMMERS, EF;WILDER, RL

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大鼠的裸体特征是以常染色体隐性方式传播的,与胸腺发育不全、T细胞缺陷和无毛有关。RNU(Rowett Nude)纯合子大鼠是研究炎症性疾病、肿瘤生长和移植排斥反应的重要模型。RNU基因座之前还没有被定位,基因产物的性质尚不清楚。为了确定该基因的定位,用3只Lew/N(NIH系Lewis大鼠)雌性大鼠与1只F344.rnu/rnu(无性体裸鼠同源Fischer大鼠)雄性同源大鼠杂交产生F1后代。建立了12对F1兄妹交配组合。共获得表型为裸鼠的F2代后代49例(共198例)。对F2DNA的连锁分析表明,裸露表型与位于染色体(Chr)10上的8个多态标记之间存在极显著的协同分离。连锁最紧密的是MYH3(胚胎、骨骼肌球蛋白重链)和SHBG(性激素结合球蛋白),两点Lod得分分别为20.2和20.0。通过多点连锁计算确定的图谱顺序和图谱距离为:RR24-(16.1 cM)-MYH3-(3.5 cM)-SHBG-(4.7 cM)-RNU-(11.9 cM)-F16F2-(24.1 cM)-CLATP(柠檬酸裂解酶)-(2.4 cM)-ACE(血管紧张素转换酶)/PPY(胰多肽)-(14.1 cM)-RR1023。RNU基因在大鼠中的位置与最近报道的NU基因在小鼠中的位置密切相关。这一发现表明,大鼠和小鼠的裸露表型源于同源基因的缺陷。
The nude trait in the rat is transmitted in an autosomal recessive manner and is associated with thymic aplasia, T-cell deficiency, and hairlessness. Congenic rats homozygous for the RNU (Rowett nude) locus are important models in the study of inflammatory disease, tumor growth, and transplant rejection. The RNU locus has not been previously mapped, and the nature of the gene product is unknown. To determine the map location of this gene, a single F344.rnu/rnu (athymic nude congenic Fischer rat) male congenic rat was bred with 3 LEW/N (NIH stock Lewis rat) female rats to produce F1 progeny. Twelve F1 brother-sister breeding pairs were established. Forty-nine phenotypically nude F2 offspring (198 total) were obtained. Linkage analysis done on F2 DNA revealed highly significant cosegregation between the nude phenotype and eight polymorphic markers located on Chromosome (Chr) 10. The tightest linkages were with: MYH3 (embryonic, skeletal myosin heavy chain) and SHBG (sex hormone-binding globulin), giving 2 point lod scores of 20.2, and 20.0, respectively. The map order and map distances, determined by multipoint linkage calculations, were: RR24-(16.1 cM)-MYH3-(3.5 cM)-SHBG-(4.7 cM)-RNU-(11.9 cM)-F16F2-(24.1 cM)-CLATP (citrate lyase ATPase)-(2.4 cM)-ACE (angiotensin converting enzyme)/PPY (pancreatic polypeptide)-(14.1 cM)-RR1023. The position of the RNU locus in the rat corresponds closely with that of the recently reported nu locus in the mouse. This finding suggests that the nude phenotype in the rat and the mouse arise from defects in homologous genes.