Table 7.

Methods of delivering Cre for cell-type targeting, labeling, and manipulation.

	Method of Cre delivery
	Targeted knock-in Cre mouse line	Transgenic Cre mouse line (not generated by homologous recombination)	Cre via AAV
Advantages	• Specific and reliable by genetic targeting to the locus of interest (higher certainty that driver activity will reflect the endogenous expression of the gene of interest)	• Cheap and easy to produce mouse lines	• Stable over time
	• Comprehensive with Cre mouse lines	• Lower Cre expression than AAV	• Spatial control: can restrict delivery to a particular region
	• Sparse if using CreER by adjusting tamoxifen dose	• Can be delivered broadly by systemic (e.g., tail vein or retro-orbital) injection
	• Can combine with viral strategies to achieve spatial control or very strong expression
	• Lower Cre expression than AAV
Disadvantages	• Time-consuming and costly to produce and maintain mouse lines	• Does not necessarily recapitulate the endogenous gene’s expression	• Expression gradients from injection site(s)
	• Genetic silencing in mouse lines can affect Cre expression	• AAV vectors increase interleukin levels in the animal
		• Sexual dimorphism can arise that does not reflect the gene’s native expression profile	• High levels of Cre protein exhibit cell toxicity
		• Transgenic animals can lose specificity over time