鼠体内选择单个基因使它失活而其他基因不受影响。这样的老鼠提供了最好的描素基因功能的方法。把将要灭活的基因分离出来并通过通过遗传工程法使它失去活性并携带标记。将这一基因注入胚胎干细胞里，少数情况下，灭活基因会与正常基因并排并取代它。这一结果可以由被灭活的基因所携带的标记所显示出来。那些携带灭活基因的胚胚胎干细胞经分离出来后注入称作胚泡的胚前组织中。胚泡又被移植入母鼠体内生长。最终老鼠的某些细胞中将含有灭活基因。适当地对这些阳性老鼠进行交配繁殖会得到含有灭活基因纯合体的老鼠。

A mouse in which a single gene of choice is inactivated or “knocked out” in a manner that leaves all other genes unaffected. Such mice provide the best way to delineate the function of a gene. The gene to be “knocked out” is first isolated and genetically engineered so that it is inactive and carries genetic “tags” within it. This genetic construct is then introduced into special cells called Embryonic Stem (ES) cells. In a small number of cases, the inactivated gene will align with the correct gene, and then replace it. This event can be traced by the genetic tags introduced into the defective gene. Those ES cells carrying the inactivated gene can then be isolated and introduced (by injection) into a pre-embryonic structure called the blastocyst. The blastocyst can then be transplanted into a female mouse to develop to term. Some of the cells in the resultant mouse will contain the inactivated gene. Appropriate breeding of the positive mice will yield a mouse in which both copies (one on each chromosome) of the gene are inactivated.