All mice Are The Same, Until They're Not

Shiva Mudide

Article URL: https://www.sciencenews.org/blog/scicurious/all-mice-are-same-until-theyre-not

Author: Bethany Brookshire

Date of Publication: January 3, 2014

Summary:

The C57 Black 6 Mouse is commonly used in the lab for scientific experiments and testing. Each Black 6 mouse should be identical to every other one, since they have been bred with their siblings for hundreds of generations. It seems like there should only be a few genetic differences left, but supposedly identical mouse strains have their differences.  Usually, these differences are mutations in DNA base pairs that accumulate in different populations. The Black 6 mouse, was established in 1921 and was originally purchased from a farm and then carefully bred to procure identical mice. In 1951, the National Institute of Health took a sub-colony of the 6J and started up its own colony, 6N mice. There now may be as 50 “substrains” of the Black 6, but none are standard. The 6J is featured in the Allen Brain Atlas and the Mouse Genome Sequencing Consortium. The 6N is the mouse for the International Knockout Mouse Consortium. To test if the two mice are identical, Joseph Takahashi and colleagues ran behavioral screens on the 6J and the 6N. In a test of the response to cocaine, The 6J mouse had twice the stimulated response to cocaine that the 6N did. Thus, when the populations diverged only 62 years ago, something had changed. They then bred the 6J and the 6N together for two generations. The second generation had an intermediate response to cocaine halfway in between the 6J and the 6N. The difference came down to a single DNA base pair in a single gene called Cyfip2. A mutation in the gene meant that the 6N had an unstable form of the Cyfip2 protein, and thus a decreased stimulant response to cocaine. Takahashi’s group found 100 other mutations in the mice. The Cyfip2 mutation itself plays a fundamental role in how neurons join to each other. It could create changes in many other areas of the brain. With just a few changes between substrains, comparing behaviors could help figure out how specific changes in genes affect behavior. Still, going forward, scientists might need to consider not just what mouse strain they use, but what mouse substrain. This shows how just one gene change, can effect the entire mouse. 

Relevance:
This article is relevant to our study of molecular genetics. More specifically it relates to on what we learned about mutations. We learned that the two main types of gene mutations are point mutations, and frameshift mutations. The mutation of Cyfip2 was most likely a frameshift mutation such as a insertion or deletion. This is because a frameshift mutation is much more drastic, affecting every amino acid coded for that follows. A mutation causing such a great difference in the reaction to cocaine would seem ambiguous if it weren't for a frameshift mutation. Furthermore, it seems like the Cyfip2 mutations altered the DNA in gametes. We learned that mutations can only be passed down to offspring if the DNA in gametes is mutated. This is because in a somatic cell mutation, the mutation stays within the body. It cannot be passed down. If DNA is mutated in the gametes, it can be passed down. Since they tested multiple 6J and multiple 6N mice, and got the same results, that means that they all had their respective version of the Cyfip2 gene. The gene must have been passed down to them through a mutation in the gametes. This article is also relevant to our study of heredity, and more specifically the section "heredity ii." We learned that incomplete dominance is when one allele is not completely dominant over the other. This could have been the case of the Cyfip2 mutation, because when bred to the second generation, they had an intermediate response to cocaine halfway between the 6J and 6N. Usually in a gene of incomplete dominance, the result of having two different alleles is a phenotype in the middle of the two homozygous phenotypes.