Mouse Knockouts



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Mouse Knockouts of SH2 domain proteins

Single Mouse Knockouts Multiple Mouse Knockouts

Single Mouse Knockouts
Targeted Gene	Phenotype	Organ and Cell types affected	Sources
ABL1	Death 1 to 2 weeks post-birth	Thymus, spleen	(Schwartzberg et al., 1991; Tybulewicz et al., 1991)
ABL2	Multiple behavioral abnormalities	Brain	(Koleske et al., 1998)
APS	Viable and fertile; hypoinsulinemia	B1 lymphocytes, adipocytes	(Iseki et al., 2004; Minami et al., 2003)
BKS	Normal	Hepatocytes	(Minoguchi et al., 2003)
BLK	Normal	None	(Texido et al., 2000)
BLNK	High incidence of pre-B cell lymphoma.	B lymphocytes	(Flemming et al., 2003; Jumaa et al., 2003)
BMX	Normal	Endocardium and arteries endothelial cells	(Rajantie et al., 2001)
BTK	XID phenotype	B lymphocytes	(Kerner et al., 1995; Khan et al., 1995)
CBL	Thymic phenotype	Thymus, T lymphocytes	(Naramura et al., 1998)
CBLB	Autoimmune encephalomyelitis	T lymphocytes	(Chiang et al., 2000)
CBLC	Normal	None	(Griffiths et al., 2003)
CRK	Normal	None	(Imaizumi et al., 1999)
CRKL	Partial embryonic lethality	Thymus	(Guris et al., 2001; Peterson et al., 2003)
CSK	Embryonic lethality at E 10-12	Neural tube	(Imamoto and Soriano, 1993; Nada et al., 1993)
DAPP1	Normal	B lymphocytes	(Fournier et al., 2003; Han et al., 2003)
FER	Healthy and fertile (Kinase-inactivating mutation)	None	(Craig et al., 2001)
FES	Viable; abnormal innate immunity	Bone marrow, myeloid cells	(Senis, Y. et al., 1999; Hackenmiller et al., 2000; Zirngibl et al., 2002)
FGR	Defective lung inflammation	Tissue and airway eosinophilia	(Lowell et al., 1994)
FRK	Normal	None	(Chandrasekharan et al., 2002)
FYN	Suckling abnormality	Olfactory bulb, hippocampus	(Yagi et al., 1993)
GADS	Healthy	T lymphocytes	(Yoder et al., 2001)
GRAP	Viable, fertile and healthy	Lymphocytes	(Shen et al., 2002)
GRB2	Embryonic lethality	Endoderm	(Cheng et al., 1998)
GRB10	30% larger in size than wildtype	Brain, liver	(Charalambous et al., 2003)
GRB14	Glucose tolerance improvement	Liver, skeletal muscle	(Cooney et al., 2004)
HCK	Normal	Macrophages	(Lowell et al., 1994 )
ITK	Normal	T lymphocytes	(Liao and Littman, 1995)
JAK1	Perinatally lethal, nursing defect	Neurons, fibroblasts, T and B lymphocytes	(Rodig et al., 1998)
JAK2	Embryonic lethality	Hematopoeitic blood cells	(Neubauer et al., 1998; Parganas et al., 1998)
JAK3	Immunodeficient; lymphopenia	Thymus, spleen, lymph nodes	(Nosaka et al., 1995; Thomis et al., 1995)
LCK	Thymic atrophy	Fetal thymus	(Molina et al., 1992 )
LNK	Splenomegaly, defects in hematopoietic lineages	Hematopoietic progenitor cells, spleen	(Takaki et al., 2000; Velazquez et al., 2002)
LYN	Hyperglobulinemic, Glomerulonephritis	B lymphocytes, mast cells	(Hibbs et al., 1995; Nishizumi et al., 1995)
MATK	Normal	None	(Hamaguchi et al., 1996)
MIST	Normal	None	(Utting et al., 2004)
NCK1	Normal	None	(Bladt et al., 2003)
NCK2	Normal	None	(Bladt et al., 2003)
PIK3R1	X-linked immunodeficiency; hypoglycemia	B lymphocytes	(Fruman et al., 1999; Suzuki et al., 1999)
PIK3R2	Hypoglycemia	Muscle	(Ueki et al., 2002)
PLCG1	Embryonic lethality between E 8.5-9.0	N/A	(Ji et al., 1997)
PLCG2	Viable, B-cell deficiency	B lymphocytes	(Wang et al., 2000)
PTPN6	Immunity and hematopoiesis defects	T lymphocytes	(Shultz et al., 1993; Van Zant and Shultz, 1989)
PTPN11	Embryonic lethality at E 10.5	Node, notochord	(Arrandale et al., 1996; Saxton et al., 1997)
RASA1	Embryonic lethality by E 10.5	Vascular system, endothelial cells	(Henkemeyer et al., 1995)
RIN1	Normal	Amygdala	(Dhaka et al., 2003)
SH2B	Growth retardation, fertility defect, insulinemia	Testis, ovaries, skeletal muscle, liver and fat	(Duan et al., 2004; Ohtsuka et al., 2002)
SH2D1A	Recapitulates X-Linked lymphoproliferative disease	T and (B) lymphocytes	(Crotty et al., 2003; Czar et al., 2001; Wu et al., 2001)
SH2D2A	Susceptible to Lupus-like autoimmune disease	T lymphocytes	(Rajagopal et al., 1999)
SHCA	Embryonic lethality by E 11.5	Heart	(Lai and Pawson, 2000)
SHCB	Normal	Sensory neurons	(Sakai et al., 2000)
SHCC	Normal	None	(Sakai et al., 2000)
SHIP	Fail to thrive with splenomegaly	Spleen, lymphoid, erthryoid, myeloid cells	(Helgason et al., 1998)
SHIP2	Resistant to dietary obesity and growth affects	Skeletal muscle, liver	(Elchebly et al., 1999; Sleeman et al., 2005 )
SLAP	Fertile and healthy	T lymphocytes	(Lowell et al., 1994; Sosinowski et al., 2001)
SLP76	Impaired viability; defective thymocyte development	T lymphocytes	(Pivniouk et al., 1998)
SOCS1	Fatty degeneration of the liver	Liver, Thymocytes	(Starr et al., 1998)
SOCS2	Gigantism	Most visceral organs	(Metcalf et al., 2000)
SOCS3	Embryonic lethality between E 11-13	Placental, blood vessel	(Marine et al., 1999; Metcalf et al., 2000; Roberts et al., 2001)
SOCS5	Normal	None	(Brender et al., 2004)
SOCS6	Normal but weigh 10% less than wild-type	N/A	(Krebs et al., 2002)
SOCS7	Healthy and fertile but die from hydrocephalus	Brain	(Krebs et al., 2004)
SRC	Defective bone remodeling and osteoporosis.	Bone osteoclast	(Soriano et al., 1991)
SRMS	Normal	None	(Kohmura et al., 1994)
STAT1	Normal but sensitive to infection	T lymphocytes, macrophages	(Meraz et al., 1996)
STAT2	Exhibit multiple defects in immune response	Fibroblasts	(Park et al., 2000)
STAT3	Embryonic lethality between E 6.5-7.5	Visceral endoderm, T lymphocytes,	(Takeda et al., 1997)
STAT4	Normal	T lymphocytes	(Kaplan et al., 1996)
STAT5A	Normal	Mammary glands	(Liu et al., 1997)
STAT5B	Decrease growth in males	Liver, mammary glands, adipose tissue	(Teglund et al., 1998)
STAT6	Normal	T and B lymphocytes	(Shimoda et al., 1996)
SYK	Perinatal lethality and blocked B-cell development	B lymphocytes	(Cheng et al., 1995; Turner et al., 1995)
TEC	Normal	B lymphocytes	(Ellmeier et al., 2000)
TNS	Normal	Kidney, muscle myoblast	(Lo et al., 1997)
TXK	Death by 102 days	Splenocytes	(Schaeffer et al., 1999)
TYK2	Normal	T lymphocytes	(Karaghiosoff et al., 2000; Shimoda et al., 2000)
VAV1	Normal	T lymphocytes	(Zhang et al., 1994)
VAV2	Normal	None	(Tedford et al., 2001)
VAV3	Normal	None	(Fujikawa et al., 2003)
YES	Normal	None	(Stein et al., 1994)
ZAP70	SCID	T lymphocytes	(Negishi et al., 1995)

Multiple Mouse Knockouts
Targeted Gene	Phenotype	Organ and Cell types affected	Sources
ABL1/ABL2	Neurulation defects	Neural tube	(Koleske et al., 1998)
APS/SH2B	Body weight increase, obesity, hyperglycemia	Adipocytes	(Li et al., 2006)
BTK/TEC	Defective lymphocyte development	B lymphocytes	(Ellmeier et al., 2000)
CBL/CBLB	Embryonic lethality at E10	T lymphocytes	(Naramura et al., 2002)
FGR/HCK	Immunodeficiency	Macrophages	(Lowell et al., 1994)
FGR/SRC	Src defects	Osteoclasts	(Lowell et al., 1996)
HCK/SRC	Two thirds die at birth; osteopetrosis	Hematopoietic cells	(Lowell et al., 1996)
ITK/TXK	Immunological defects	T lymphocytes	(Schaeffer et al., 1999)
LCK/FYN	T cell development defect	T lymphocytes, Dendritic cells	(van Oers et al., 1996)
NCK1/NCK2	Embryonic lethality at E 9.5	Notochord	(Bladt et al., 2003)
SHCB/SHCC	Normal but defective neural development	Superior Cervical ganglia (SCG) neurons	(Sakai et al., 2000)
STAT5A/STAT5B	Infertile female mice	Ovaries, mammary glands	(Teglund et al., 1998)
SYK/ZAP70	T cell development defect	Thymocytes	(Cheng et al., 1997)
VAV1/VAV2/VAV3	Defective lymphocyte development	T and B lymphocytes	(Fujikawa et al., 2003)

SH2_KOMice.pdf

(196KB)

Targeted gene disruptions have been completed for a large subset of SH2 proteins, yielding a wide range of phenotypes. In some cases, compensatory mechanisms have required the disruption of multiple members of a family in order to expose a phenotype.