Table 2.

Pros and cons of genetically engineered mice (GEM).

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 tissue	-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