Geisterfer-Lowrance A A, Christe M, Conner D A, Ingwall J S, Schoen F J, Seidman C E, Seidman J G
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Science. 1996 May 3;272(5262):731-4. doi: 10.1126/science.272.5262.731.
A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg 403 --> Gln mutation into the alpha cardiac myosin heavy chain (MHC) gene. Homozygous alpha MHC 403/403 mice died 7 days after birth, and sedentary heterozygous alpha MHC 403/+ mice survived for 1 year. Cardiac histopathology and dysfunction in the alpha MHC 403/+ mice resembled human FHC. Cardiac dysfunction preceded histopathologic changes, and myocyte disarray, hypertrophy, and fibrosis increased with age. Young male alpha MHC 403/+ mice showed more evidence of disease than did their female counterparts. Preliminary results suggested that exercise capacity may have been compromised in the alpha MHC 403/+ mice. This mouse model may help to define the natural history of FHC.
通过将精氨酸403突变为谷氨酰胺引入α心肌肌球蛋白重链（MHC）基因，构建了家族性肥厚型心肌病（FHC）小鼠模型。纯合子αMHC 403/403小鼠出生后7天死亡，久坐不动的杂合子αMHC 403/+小鼠存活1年。αMHC 403/+小鼠的心脏组织病理学和功能障碍与人类FHC相似。心脏功能障碍先于组织病理学变化，且心肌细胞排列紊乱、肥大和纤维化随年龄增加。年轻雄性αMHC 403/+小鼠比雌性小鼠表现出更多的疾病迹象。初步结果表明，αMHC 403/+小鼠的运动能力可能受损。该小鼠模型可能有助于确定FHC的自然病程。
