In ALS mice model with mutant SOD1 - there are use of transgenic mice, with insert of human mutant SOD1.

Why is that? Why not to mutate directly mice SOD1 ?

In transgenic mice, after few generations these human gene thrown out and not present any more.. Why thrown out? Is the second question.

Looking for an answer for a while. Thanks a lot.

  • $\begingroup$ Have you done any research what-so-ever on humanized mice and transgenics? You are manipulating the gene one way or the other. Starting with a null background then adding the human gene of interest through homologous recombination is how you produce an animal that can actually give you data for the question you are investigating. Your third paragraph is completely wrong. Doing speed transgenics it will take you about 4 generations to breed the humanized allele into a homozygous state in the animal. Once it is homozygous, you can then start to analyze the data you are producing. $\endgroup$ – AMR Oct 25 '15 at 14:12

The use of a mouse with the replacement of one of its genes with a human version is to better mimic the human disease phenotype, or to prove something about the biology of the human phenotype with research that can't be conducted in humans.

Genes and their corresponding proteins or RNA usually differ somewhat between mouse and humans. If you wanted to study whether a certain SNP in a gene (found in humans) was the reason for part of your phenotype, you may want to use transgenic mice to test hypotheses with different exacerbations (treatments). One way to do this is to create a mouse with the human gene replacing the mouse gene, and another mouse with the human gene containing the trait-linked SNP.

If you tried to do this with the mouse gene, you couldn't be sure that the same SNP would have the same functional consequences. If you didn't remove the endogenous gene from the mouse before replacing it with the human version, you would never be sure if observed experimental phenotypes weren't confounded by both copies of the gene and their corresponding gene products being active in the same animal.

In your example, with SOD1 and ALS, creating a humanized mouse with human SOD1 allows researchers to more fully study the same protein product made in humans, while giving the mouse treatments that would be unethical in humans.

Your understanding in your last part is incorrect. Mice don't lose genes after a few generations.

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