Table 1.

Animal models of Ras/ERK signaling in T cell development and function

Mouse model	Developmental effect	Refs
Grb2+/−	Normal positive selection Defective negative selection	[46]
Grb2(T)−/−	Defective positive selection Defective negative selection	[51]
Rasgrp1−/−	20% reduction in thymocyte cellularity Mild defect in β selection, but normal α-CD3ε induced proliferation in Rag2−/− Defective positive selection Normal negative selection	[16,26,27,34,38]
Rasgrp4−/−	Normal T cell development	[38]
Rasgrp1/Rasgrp4 DKO	80% reduction in thymocyte cellularity Defective βselection Possible defect in positive selection (more than RasGRP1−/−) due to further reduction in peripheral T cell numbers Negative selection not examined	[38]
Sos1(T)−/−	50% reduction in thymocyte cellularity Proliferative defect at β-selection checkpoint/defective α-CD3ε-induced proliferation in Rag2−/− Normal positive and negative selection	[26,27]
Sos2−/−	Normal T cell development, did not modulate Sos1 or RasGRP1 knockout phenotype	[27]
Sos1(T)/Rasgrp1 DKO	70–90% reduction in thymocyte cellularity Defective βselection Defective positive and negative selection	[27]
Rasgrf2−/−	Normal T cell development	[37]
Rasa1−/− (p120RasGAP deficient)	Normal β-selection Enhanced MHC class II-mediated positive selection Normal negative selection Reduced IL-7-mediated survival of naïve peripheral CD4+ and CD8+ lymphocytes	[71]
Nras−/−	Normal positive and negative selection Reduced antiviral responses Impaired TH1 differentiation/INFγ responses	[72,73]
Hras−/−	Normal positive and negative selection Impaired TH1 differentiation/INFγ responses	[72]
Mapk3−/− (ERK1 deficient)	Normal β selection Mild defect in positive selection Normal negative selection	[7,9]
Mapk1−/− (ERK2 deficient)	50% reduction in thymocyte cellularity Defective β selection Defective positive selection, negative selection not tested Impaired TH1 differentiation Impaired T cell proliferation and survival	[7,74,75]
Mapk3/Mapk1 DKO (ERK1 and ERK2 deficient)	75% reduction in thymocyte cellularity Defective β selection Defective positive selection Normal negative selection	[7,47]
Lat-Y136F	Defective β selection Defective positive and negative selection Develop an ERK-dependent TH2 lymphoproliferative disease dependent, in part, on signaling via Bam32, RasGRP1, and Sos1/2	[11,12,54,55]

INF, interferon.