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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 \(\mathrm{X}\) and \(\mathrm{Y}\) chromosomes in sex determination and sexual differen- tiation in mammals? Can you devise an experiment, assuming you can "genetically engineer" the chromosomes of mice, to test and confirm your explanation?

Short Answer

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Answer: The Tfm gene product might be involved in the testosterone signaling pathway, regulating sexual differentiation. The Y chromosome could initiate testes development, while the Tfm gene on the X chromosome plays a significant role in further sexual differentiation. An experiment can be designed using four groups of genetically engineered mice with different combinations of X/Y chromosomes and Tfm mutation. Observing their development, analyzing hormone responses, and comparing results will help determine the role of Tfm gene product and X/Y chromosomes in sex determination.

Step by step solution

01

Hypothesis: Role of Tfm Gene and X/Y Chromosomes in Sex Determination

Based on the information given, we could hypothesize that the Tfm gene product is involved in the pathway that processes the testosterone hormone signaling. By eliminating the normal testosterone response, the mouse only develops testes and remains phenotypically female. Thus, the sex determination during embryonic development could be predominantly regulated by the Tfm gene product and its function in the testosterone signaling pathway. Furthermore, the presence of Y chromosome may be responsible for the initiation of testes development, whereas Tfm gene in the X chromosome plays a crucial role in the further sexual differentiation.
02

Experiment Design: Genetically Engineered Mice to Confirm Hypothesis

To test the hypothesis, we can design an experiment using genetically engineered mice with altered Tfm gene product and X/Y chromosomes. The following steps describe the experiment: 1.
03

Create Genetically Engineered Mice Groups

Dividing the mice into four groups: - Group A: Normal XX mice (Control Group) - Group B: Normal XY mice (Control Group) - Group C: XX mice with Tfm gene (Tfm-modified Group) - Group D: XY mice with Tfm gene (Tfm-modified Group) 2.
04

Monitor Mouse Development

Observe the development of the mice in each group, specifically noting sex determination and sexual differentiation during development. Record data on the development of the gonads (testes or ovaries) and external genitalia (male or female). 3.
05

Analyze Hormone Responses

Perform hormone assays to measure testosterone levels and its response in each group. This will provide data on how the presence of Tfm gene and X/Y chromosomes affect hormonal production and responsiveness. 4.
06

Assess Results

Compare the data from each group and determine patterns in sex determination and sexual differentiation across the groups. If the Tfm-modified mice show different sexual development from the control groups, particularly Group D (XY Tfm-mutant mice) with female external genitalia and testes formation, this would support our hypothesis. By performing this experiment, we can understand the role of the Tfm gene product and the X/Y chromosomes in sex determination and differentiation in mice. If the hypothesis is confirmed, we would conclude that the Tfm gene product plays a crucial role in testosterone response during sexual differentiation, and the presence of Y chromosome is responsible for testes initiation.

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Most popular questions from this chapter

In this chapter, we have focused on sex differentiation, sex chro- mosomes, and genetic mechanisms involved in sex determination. At the same time, we found many opportunities to consider the methods and reasoning by which much of this information was acquired. From the explanations given in the chapter, you should answer the following fundamental questions: (a) How do we know that in humans the X chromosomes play no role in sex determination, while the Y chromosome causes maleness and its absence causes femaleness? (b) How did we originally (in the late 1940 s) analyze the sex ratio at conception in humans, and how has our approach to studying this issue changed in \(2015 ?\) (c) How do we know that \(X\) chromosomal inactivation of either the paternal or maternal homolog is a random event during early development in mammalian females? (d) How do we know that Drosophila utilizes a different sexdetermination mechanism than mammals, even though it has the same sex-chromosome compositions in males and females?

In chickens, a key gene involved in sex determination has recently been identified. Called \(D M R T 1\), it is located on the \(Z\) chromosome and is absent on the W chromosome. Like SRY in humans, it is male determining. Unlike \(S R Y\) in humans, however, female chickens (ZW) have a single copy while males (ZZ) have two copies of the gene. Nevertheless, it is transcribed only in the developing testis. Working in the laboratory of Andrew sinclair (a co-discoverer of the human SRY gene), Craig Smith and colleagues were able to "knock down" expression of \(D M R T 1\) in \(\mathrm{ZZ}\) embryos using RNA interference techniques (see Chapter 15 ). In such cases, the developing gonads look more like ovaries than testes [Nature 461: 267 (2009)]. What conclusions can you draw about the role that the DMRTI gene plays in chickens in contrast to the role the SRY gene plays in humans?

Describe how nondisjunction in human female gametes can give rise to Klinefelter and Turner syndrome offspring following fertilization by a normal male gamete.

A group of scientists developing an XX zygote in vitro are curious to see the impact of certain chemicals on the development of the said organism. They incubate the zygote with the help of testosterone and some transcription factors, which are usually produced by the activity of the Y chromosome. They discover that the zygote develops into a sterile female with masculinized reproductive organs. Explain why this happens.

As related to sex determination, what is meant by (a) homomorphic and heteromorphic chromosomes; and (b) isogamous and heterogamous organisms?

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