Tokumitsu M, Ogawa K
Department of Pathology, Asahikawa Medical College, Japan.
Genome. 1994 Dec;37(6):1022-6. doi: 10.1139/g94-145.
Strain variation in the mouse p53 gene sequences was investigated in various regions of the gene in 14 inbred strains of laboratory mice and one Japanese wild mouse strain (Mus musculus molossinus Mishima, M. MOL-MSM). Nucleotides within p53 introns 1 and 7, found to be identical in 10 of the laboratory strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, CBA/J, CE/J, NZB, and SWR/J), were substituted for other nucleotide sequences in common with M. MOL-MSM and the four other strains (DBA/1J, DBA/2J, I/LnJ, and P/J). The latter were documented to have originated from a common ancestor. These observations thus suggested the possibility that the p53 gene may have become substituted by outcrossing of this ancestral strain with Asian mice; this is presumably related to the documentation that Japanese mice brought to western countries were used as laboratory mice early in this century. To establish p53 gene heterozygosity, female C3H/HeJ and male DBA/2J mice were mated to produce F1 hybrids (C3D2F1). Electrophoresis of PCR fragments including polymorphic regions with or without restriction enzyme digestion, allowed clear distinction of paternal and maternal p53 alleles. These markers, therefore, should be useful for studying the loss of heterozygosity of the p53 gene during the carcinogenic process.
在14种近交系实验小鼠和1种日本野生小鼠品系(小家鼠三岛亚种,M. MOL - MSM)的p53基因不同区域,研究了该基因的品系变异。p53基因内含子1和7中的核苷酸,在10种实验小鼠品系(129/J、A/J、AKR/J、BALB/cJ、C3H/HeJ、C57BL/6J、CBA/J、CE/J、NZB和SWR/J)中是相同的,但在与M. MOL - MSM及其他4种品系(DBA/1J、DBA/2J、I/LnJ和P/J)中被其他核苷酸序列所取代。后4种品系被证明起源于一个共同祖先。这些观察结果因此提示,p53基因可能通过该祖先品系与亚洲小鼠的杂交而被取代;这大概与本世纪初带到西方国家的日本小鼠被用作实验小鼠的记录有关。为了建立p53基因杂合性,将雌性C3H/HeJ小鼠和雄性DBA/2J小鼠交配产生F1代杂种(C3D2F1)。对包含多态性区域的PCR片段进行电泳,无论有无限制性酶切,都能清晰区分父本和母本的p53等位基因。因此,这些标记物对于研究致癌过程中p53基因杂合性的丧失应该是有用的。