CANE Paper - https://www.sciencedirect.com/science/article/pii/S0896627316307164?via%3Dihub#bib1

Sure, I'll break down the provided passage and answer each of your questions:

  1. What is "knockin mouse (Fos-2A-dsTVA)"?

    A "knockin mouse" refers to a genetically modified mouse in which a specific gene or sequence has been inserted (or "knocked-in") into a particular location in the mouse genome. The designation "Fos-2A-dsTVA" provides information about the specific genetic modification made. In this mouse, the Fos gene (which is associated with neural activity) has been engineered to be linked to another sequence encoding for 2A (a self-processing peptide) and dsTVA (a version of the TVA receptor that is less stable than the typical version).

  2. "Activity-induced Fos expression triggers co-expression of a destabilized TVA (dsTVA) receptor". Does this mean when fos is expressed dsTVA is also expressed?

    Yes, that's correct. The sentence means that when the Fos gene is activated due to neural activity (hence "activity-induced"), it results in the expression of both Fos protein and the dsTVA receptor. This co-expression is facilitated by the 2A peptide, which I'll explain more in the next point.

  3. "2A is a self-processing peptide that enables Fos and dsTVA to be co-translated." What is this self-processing peptide?

    The 2A peptide originates from certain viruses and has a unique ability: when proteins are translated (synthesized) from genes that have the 2A sequence inserted between them, the 2A peptide causes a "cleavage" event during the translation process. This results in the production of two separate proteins from a single translation event. In other words, instead of one long fusion protein being produced, two distinct proteins are made, essentially "co-translated" from a single mRNA molecule.

    In the context of the passage you provided, the 2A peptide has been utilized to ensure that when the Fos gene is expressed due to neural activity, both Fos and dsTVA proteins are produced as distinct entities (rather than a fused protein). This allows for the specific targeting of these neurons using the dsTVA receptor and the pseudotyped viruses mentioned.

Briefly

In activated neurons Fos Gene is expressed.

When Fos is expressed, it is a nice idea to co-express another gene for marker.

Suppose u want to express TVA gene along with Fos. Keep 2A between them. when fos is expressed 2 A will cause TVA to also express.

Now, you want a virus(say Rabies Virus) to infect only in the cells where Fos is expressed. So, you wrap the virus in an envelop called EnvA. When EnvA wrapped virus binds to TVA, only then virus can enter the cytoplasm of the cell.

EnvA wrapped virus when finds TVA will help the virus to enter the cell