Seyfried T N, Yu R K, Glaser G H
Genetics. 1980 Mar;94(3):701-18. doi: 10.1093/genetics/94.3.701.
The inheritance of susceptibility to audiogenic seizures (ASs) was studied in the C57BL/6J (B6) and DBA/2J (D2) progenitor strains, their reciprocal F(1) hybrids, backcross generations and in 21 B6 x D2 recombinant inbred (RI) strains of mice at 21 days of age. All of the D2 mice tested experienced ASs, whereas none of the B6 mice responded to the sound. Although 23% of the F(1) mice experienced wild running, they were generally as resistant to ASs as their B6 parents. Mice of the F(1)x B6 backcross generation were also resistant to ASs. In the F(1)x D2 backcross generation, however, a significant preponderance (72%) of AS-susceptible mice was found. No significant association was observed between any of the four coat-color phenotypes that were segregating in this generation and susceptibility to ASs. A continuous distribution of mean seizure severity scores and several new audiogenic response phenotypes, distinctly different from the phenotypes of either progenitor strain, were found among the 21 RI strains. These and the results from the F(1)x D2 backcross generation suggest that the difference in AS susceptibility between 21-day-old B6 and D2 mice cannot be under the control of a single locus. In addition, no association was found between AS susceptibility and the chromosome 4 markers Lyb-2, Mup-1 and b among the 21 RI strains. An association was observed, however, between AS susceptibility and the Ah locus. Several of the RI strains that were AS resistant at 21 days of age became AS susceptible as adults. One RI strain was susceptible to ASs at both young and adult ages. The B6, D2 and F(1) mice were completely resistant to ASs at adult ages. Genetic differences were found among the RI strains for the incidence, onset, duration, and type of severity of ASs. A remarkable amount of phenotypic variability in the audiogenic response, which can be attributed only to the influence of environmental factors, occurred within several of the RI strains. A multiple-factor mode of inheritance involving a physiological threshold can account for our observations.
在C57BL/6J（B6）和DBA/2J（D2）亲本品系、它们的正反交F(1)杂种、回交世代以及21个B6×D2重组近交（RI）品系的小鼠21日龄时，研究了对听源性惊厥（ASs）易感性的遗传情况。所有测试的D2小鼠都经历了ASs，而所有B6小鼠对声音均无反应。虽然23%的F(1)小鼠出现狂奔，但它们对ASs的抗性通常与其B6亲本一样。F(1)×B6回交世代的小鼠对ASs也有抗性。然而，在F(1)×D2回交世代中，发现AS易感性小鼠占显著优势（72%）。在该世代中分离的四种毛色表型中的任何一种与ASs易感性之间均未观察到显著关联。在21个RI品系中发现平均惊厥严重程度评分呈连续分布，并且有几种新的听源性反应表型，与任一亲本品系的表型明显不同。这些以及F(1)×D2回交世代的结果表明，21日龄B6和D2小鼠之间AS易感性的差异不可能受单个基因座控制。此外，在21个RI品系中，未发现AS易感性与4号染色体标记Lyb-2、Mup-1和b之间存在关联。然而，观察到AS易感性与Ah基因座之间存在关联。一些在21日龄时对AS有抗性的RI品系成年后变得对AS易感。一个RI品系在幼年和成年时均对ASs易感。B6、D2和F(1)小鼠在成年时对ASs完全有抗性。在RI品系中发现了ASs在发生率、发作、持续时间和严重程度类型方面的遗传差异。在几个RI品系中出现了仅可归因于环境因素影响的听源性反应中显著的表型变异性。涉及生理阈值的多因素遗传模式可以解释我们的观察结果。
