Chromosomal localization of the loci responsible for dystrophic cardiac calcinosis in DBA/2 mice
Chromosomal localization of the loci responsible for dystrophic cardiac calcinosis in DBA/2 mice
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DOI：
10.1006/geno.1999.5862
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发表时间：
1999-07-01
期刊：
影响因子：
4.4
通讯作者：
Chang, B
中科院分区：
文献类型：
--
作者：
Brunnert, SR;Shi, S;Chang, B
营养不良性心脏钙质沉着症(DCC)发生在某些近交系小鼠身上，包括DBA/2和C3WHe，通常是成年动物尸检时的一种偶发病变。对DBA/2小鼠DCC病因的初步遗传学研究表明，DCC是一种常染色体隐性遗传性状，涉及三个或四个未连锁的基因。为了进一步研究DCC的遗传学，我们用冻融损伤的方法造成心肌细胞死亡来诱导DCC。用3个近交系小鼠(DBA/2J和C3H/HeJ，DCC易感品系；C57BL/6J，DCC抗性品系)配制了3个杂种，比较了DCC发生的遗传因素。我们发现DBA/2和C3H/He小鼠具有相同的基因模式(S)，这是导致DCC的原因。通过对DBA/2和C57BL/6小鼠的回交连锁分析，我们确定至少有一个隐性基因座与DCC有关。对回交数据的单倍型分析表明，该隐性基因座位于7号染色体上，距着丝粒远20.5 cM。对dyscalc1的可能候选基因进行了讨论。进一步了解这些突变基因的结构和功能将有助于解释DCC的分子发病机制。(C)1999年学术出版社。
Dystrophic cardiac calcinosis (DCC) occurs in certain inbred strains of mice, including DBA/2 and C3W He, and is generally found as an incidental lesion in adult animals at necropsy. Preliminary genetic studies into the cause of DCC have been performed in DBA/2 mice and suggest that DCC is inherited as an autosomal recessive trait involving three or four unlinked genes. To investigate the genetics of DCC fur ther, we produced myocardial cell death by freeze-thaw injury to induce DCC. Experiments were conducted with three F1 hybrids made using; three inbred strains of mice (DBA/2J and C3H/HeJ, DCC susceptible strains; C57BL/6J, DCC-resistant strain) to compare the genetic factors in the development of DCC. We found that DBA/2 and C3H/He mice share the same gene pattern(s) that is responsible for DCC. We determined by backcross linkage analysis in DBA/2 and C57BL/6 mice that at least one recessive locus is responsible for DCC. A haplotype analysis of the backcross data demonstrated that the recessive locus, designated dyscalc1, is located on Chromosome 7, 20.5 cM distal to the centromere. The likely candidate genes for dyscalc1 are discussed. Further understanding of the structure and function of these mutant genes will be beneficial in explaining the molecular pathogenesis of DCC. (C) 1999 Academic Press.