Table 2 Pros and cons of genetically engineered mice (GEM).

From: The evolution of preclinical models for myelodysplastic neoplasms

Technique

Pros

Cons

Transgenic using ubiquitous promoter

Initial technique used to generate GEM

-Random integration effect

-Ubiquitous, non-physiologic expression

Transgenic using tissue specific promoter

Tissue specific expression

-Random integration effects

-Expression may be non-physiologic

Homologous recombination “knock-out”

Useful for gene inactivation

-Vector, targeting can be challenging, unpredictable.

-Gene inactivated in all tissues.

-CRISPR improvement.

Homologous recombination “knock-in”

Express mutant cDNA, fusion gene

-Same as knock-out.

Physiologic expression from endogenous promoter.

-Expression of mutant in non-relevant tissue (e.g. ldh2 KI)

Conditional knock-out/knock-in plus

Target knockout to specific tissueView full size image

-More complex breeding.

Tissue specific Cre (trigger for event)

-Tissue specific expression may be "leaky"

Conditional knock-out/knock-in plus

Trigger Cre expression post-natal

-More complex breeding

time specific Cre (eg, Mx1, CreERT2)

-Time specific expression may be leaky