Training: Using Conditional Transgenic Models

This course is designed for anyone working with conditional mouse models, including the Cre-Lox system and alternative recombinase platforms such as Flp, Dre, and Vika. These technologies provide researchers with the ability to manipulate gene expression in a spatially and/or temporally controlled manner, enabling precise investigation of biological processes that cannot be interrogated using traditional constitutive knockout models.

By allowing genes to be selectively turned on or off in specific tissues, cell types, or developmental stages, conditional systems offer powerful means to dissect the roles of individual genes within complex physiological networks. Moreover, combining multiple recombinase systems expands the experimental possibilities even further – for example, enabling the controlled exchange of a wild type exon for a mutant variant at a defined point in time to model disease progression with exceptional precision.

However, the intricate mechanisms underlying conditional systems make them particularly vulnerable to errors and misinterpretation.

While the biology behind these approaches is elegant, in practice there are numerous pitfalls that can compromise experimental outcomes. Many of these issues are not immediately apparent from the literature on conditional models, nor are they always obvious within an experiment unless you know what to look for. Consequently, researchers may unknowingly draw inaccurate conclusions, with errors that can propagate and compromise downstream studies.

This course aims to equip trainees with a clear understanding of how these models function biologically, as well as the practical ways in which they can fail. We will cover how to anticipate and control for confounding effects, how to troubleshoot unexpected results, and how to proceed when a model does not behave as expected.

Who is this for?

Anyone who is using or planning to use conditional models, that has previous knowledge of advanced mouse genetics, including researchers, PhD students and colony managers.

After this course, you will be able to:

• Understand the basic principles of conditional transgenesis
• Understand how cre expressing and floxed alleles are produced and the potential impact on the experimental outcome
• Identify the advantages and challenges of these systems
• Analyse recombinase (Cre) expression
• Understand how to establish colonies for conditional transgenesis and the importance of background strain within this
• Plan breeding schemes with consideration of control strategies and cohort numbers

Using Conditional Transgenic Models | Mary Lyon Centre