鼠體內選擇單個基因使它失活而其他基因不受影響。這樣的老鼠提供了最好的描素基因功能的方法。把將要滅活的基因分離出來并通過通過遺傳工程法使它失去活性并攜帶標記。將這一基因注入胚胎干細胞里，少數情況下，滅活基因會與正常基因并排并取代它。這一結果可以由被滅活的基因所攜帶的標記所顯示出來。那些攜帶滅活基因的胚胚胎干細胞經分離出來后注入稱作胚泡的胚前組織中。胚泡又被移植入母鼠體內生長。最終老鼠的某些細胞中將含有滅活基因。適當地對這些陽性老鼠進行交配繁殖會得到含有滅活基因純合體的老鼠。

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.