Table 2.

Mouse models of Rho GTPase function. Compiled above is a list of Rho GTPases, the mouse models available to study them, and the vascular-associated phenotypes observed in these mice. Where a Cre driver is indicated, researchers utilized a conditional allele (flox/flox construct). KO = knockout, N/A = no available mouse line to our knowledge.

Rho GTPase	Cre Driver	Phenotype	Citation
Cdc42	Full KO	Embryonic lethal E7.5, with obvious defects as early as E5.5	[34]
	Tie2-Cre,	Embryonic lethal by E9–10; angioblast coalescence and lumenogenesis are blocked	[35]
	Cdh5-CreERT2	Deleted at E11.5—widespread hemorrhaging, failure of EC polarization and lumenogenesis, defects in vessel integrity, actin organization, and cell–ECM adhesion; Deleted from Post-natal day (P) 0–4 —required for angiogenic growth in retina but not for existing vessel stability	[35]
RhoQ	N/A	No information available
RhoJ	Full KO	Mice viable and fertile; delay in radial growth of retinal vasculature and an increase in empty sleeves	[36]
	Full KO	Mice viable; decrease in tumor angiogenesis	[37]
RhoU	N/A	N/A
Rac1	Full KO	Embryonic lethal by E9.5	[38]
	Tie2-Cre	Embryonic lethal by E9.5–10.5—improper development of major vessels and lack of small branched vessels	[39]
	Cdh5-CreERT2	Embryonic deletion (E10.5)—vessel hemorrhaging and decreased vascular area and branch points; Postnatal deletion (P1–P3)—decreased vascular area and branch points, defective angiogenic sprouting, decreased vertical blood vessel sprouting in retina	[40]
Rac2	Full KO	Mice viable and fertile; decrease in sprouting from aortic ring assay, decrease in vascularization of ischemic hindlimb and Matrigel plug assay	[41]
Rac3	Full KO	Mice viable and fertile; ECs not studied	[42]
RhoG	Full KO	Mice viable and fertile; ECs not studied	[43]
RhoBTB1	N/A	N/A
RhoBTB2	N/A	N/A
RhoBTB3	Full KO	Some lethality (homozygous weanlings present at 9.2%), mice are viable with reduced size	[44]
RhoA	Cdh5-CreERT2	Knockout at 4–6 weeks postnatal increases vessel barrier function and prevents passive cutaneous anaphylaxis	[45]
RhoB	Full KO	Mice viable and fertile with reduced size; defective angiogenesis in postnatal retina with tip cells lacking cytoplasmic extensions; decrease in angiogenesis in response to wounding, decrease in pathological angiogenesis in retina after hypoxia	[11,46]
RhoC	Full KO	Mice viable and fertile, ECs not studied	[47]
Rnd1	N/A	N/A
Rnd2	N/A	N/A
Rnd3 (RhoE)	Full KO	Heterozygote mice are viable but prone to heart failure after pressure overload and are predisposed to hemodynamic stress; heterozygote mice present dilated cardiomyopathy with heart failure and impaired angiogenesis; one report of full KO causes hydrocephaly; another report of full KO causes embryonic lethality from cardiac arrhythmia	[48,49]
RhoD	N/A	N/A
RhoF (Rif)	Full KO	Mice viable, no external abnormalities, ECs not studied	[50,51]