What is a tissue-specific knockout mouse and an inducible knockout mouse?

biology.hunter.cuny.edu/molecularbio/.../Inducible%20Cre.pdf\

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i cannot access the link; can you please post the full link

http://docs.google.com/viewer?a=v&q=cache:ga2vRuV5zKEJ:biology.hunter.cuny.edu/molecularbio/Class%2520Materials%2520Spring%25202011%2520BIol302/Lecture%252023/Inducible%2520Cre.pdf+inducible+knockout+mouse+hunter+cuny&hl=en&gl=us&pid=bl&srcid=ADGEESj77zc22763NwfZJx1JrNqYD_4uKCrGYz0kq5L12ELZKw6BncjHaZ39TzdC2qmTEKXq5a9NWN2nYkOE7Ui3gcXPvwK8npQXRhHHq2CsspvawpBf5xC8LGZ5IE2A6rcwGIzlIstG&sig=AHIEtbSGB-I03DRel9fB-Qi5NZrL5ToWwg

A tissue-specific knockout mouse is a genetically modified mouse model in which a specific gene is inactivated or "knocked out" in specific tissues or organs of interest. This is achieved by using techniques such as gene targeting or CRISPR-Cas9 technology to disrupt the functioning of the gene in those specific tissues. The aim is to understand the role of that gene in a particular tissue or organ by observing the consequences of its loss.

To generate a tissue-specific knockout mouse, researchers typically use a tissue-specific promoter to drive the expression of a recombinase enzyme such as Cre. The recombinase enzyme recognizes specific DNA sequences called loxP sites that flank the target gene. When the recombinase enzyme is produced in a specific tissue, it catalyzes a recombination event between the two loxP sites, resulting in the excision of the target gene. This way, the target gene is only knocked out in the tissues where the recombinase is active.

On the other hand, an inducible knockout mouse is a genetically modified mouse model in which the gene of interest can be selectively inactivated at a specific time point or in response to an external stimulus. This provides researchers with greater control over the timing and extent of gene inactivation.

To generate an inducible knockout mouse, researchers use a combination of tissue-specific promoters and inducible systems such as the tetracycline-responsive system (Tet-On/Tet-Off) or the Cre-ER system. In the Tet-On/Tet-Off system, the expression of the target gene can be controlled by adding or removing a specific chemical, such as doxycycline, from the mouse's diet. This allows researchers to switch the gene activity on or off when desired. In the Cre-ER system, the Cre recombinase enzyme is fused to a modified estrogen receptor, making it responsive to tamoxifen or other estrogen receptor ligands. Administration of tamoxifen activates Cre recombinase, leading to gene inactivation.

In summary, a tissue-specific knockout mouse allows researchers to study the effects of gene inactivation in specific tissues or organs, while an inducible knockout mouse provides control over the timing and extent of gene inactivation. Both mouse models are valuable tools in understanding gene function and disease mechanisms.