In mice, the X-linked dominant mutation Testicular feminization (Tfm) eliminates the normal response to the testicular hormone testosterone during sexual differentiation. An XY mouse bearing the \(T f m\) allele on the \(X\) chromosome develops testes, but no further male differentiation occurs-the external genitalia of such an animal are female. From this information, what might you conclude about the role of the Tfm gene product and the X and \(Y\) chromosomes in sex determination and sexual differentiation in mammals? Can you devise an experiment, assuming you can "genetically engineer" the chromosomes of mice, to test and confirm your explanation?

The Tfm mutation is an X-linked dominant mutation, meaning that it is present on the X chromosome and its presence leads to the manifestation of the abnormality irrespective of the presence or absence of a normal allele. In this case, the Tfm mutation leads to the elimination of the response to testosterone during sexual differentiation. Mice with the Tfm mutation on their X chromosome develop testes, but their external genitalia are female.

The presence of the Tfm mutation suggests that the Tfm gene product, which is most likely a receptor for testosterone or a molecule involved in its signal transduction pathway, plays a critical role in sexual differentiation in mammals. The Y chromosome contributes to determining the sex of the individual (XY for males, XX for females), while the X chromosome, specifically the Tfm gene, is crucial for the normal progress of sexual differentiation by ensuring proper response to testosterone. In the absence of functional Tfm, sexual differentiation is disrupted, and the individuals display female external genitalia despite having testes.

To test our hypothesis, we can design an experiment that involves genetically engineering mice and analyzing their sexual differentiation. We can perform the following steps: 1. Create three groups of mice: one with normal X and Y chromosomes (control group), one with the Tfm mutation on their X chromosome, and one with the Tfm mutation on their X chromosome but also with an extra, engineered copy of the correct Tfm gene elsewhere in the genome. 2. Allow the mice to develop normally and observe the sexual differentiation process. 3. Compare the outcomes of sexual differentiation in each group. Our hypothesis is that the control group will have normal sexual differentiation, the Tfm mutation group will have female external genitalia and testes, and the group with the extra functional copy of the Tfm gene will have normal sexual differentiation. This would confirm that the Tfm gene product is critical in sexual differentiation and that the presence of a functional copy of the gene allows for normal differentiation despite the presence of the Tfm mutation on the X chromosome.