Mouse Knockout

SH2 domain proteins have been extensively studied for their roles in invertebrate and mammalian development.  The genes for 81 SH2 containing proteins have been disrupted in mice.  

Knockout Phenotype Organs and cell types affected Source Pubmed ID
Abl1 Death 1 to 2 weeks post-birth Thymus, spleen (Schwartzberg et al., 1991; Tybulewicz et al., 1991) 2065353, 2065352
Abl2 Multiple behavioral abnormalities Brain (Koleske et al., 1998) 9883720
Aps Viable and fertile; hypoinsulinemia B1 lymphocytes, adipocytes (Iseki et al., 2004; Minami et al., 2003) 14766215, 14578283
Bks Normal Hepatocytes (Minoguchi et al., 2003) 12540842
Blk Normal None (Texido et al., 2000) 10648608
Blnk High incidence of pre-B cell lymphoma. B lymphocytes (Flemming et al., 2003; Jumaa et al., 2003) 12436112,  12761551
Bmx Normal Endocardium and arteries endothelial cells (Rajantie et al., 2001) 11416142
Btk XID phenotype B lymphocytes (Kerner et al., 1995; Khan et al., 1995) 7552995, 7552994
Cbl Thymic phenotype Thymus, T lymphocytes (Naramura et al., 1998) 9861006
Cblb Autoimmune encephalomyelitis T lymphocytes (Chiang et al., 2000) 10646609
Cblc Normal None (Griffiths et al., 2003) 14560016
Crk Normal None (Imaizumi et al., 1999) 10600543
Crkl Partial embryonic lethality Thymus (Guris et al., 2001; Peterson et al., 2003) 11242111
Csk Embryonic lethality at E 10-12 Neural tube (Imamoto and Soriano, 1993; Nada et al., 1993) 7685657, 8513497
Dapp1 Normal B lymphocytes (Fournier et al., 2003; Han et al., 2003) 14588241, 14563325
Fer Healthy and fertile (Kinase-inactivating mutation) None (Craig et al., 2001) 11134346
Fes Viable; abnormal innate immunity Bone marrow, myeloid cells (Hackenmiller et al., 2000) 11021537
Fgr Defective lung inflammation Tissue and airway eosinophilia (Lowell et al., 1994) 8125254
Frk Normal  None (Chandrasekharan et al., 2002) 12077350
Fyn Suckling abnormality Olfactory bulb, hippocampus (Yagi et al., 1993) 8264796
Gads Healthy T lymphocytes (Yoder et al., 2001) 11239162
Grap Viable, fertile and healthy Lymphocytes (Shen et al., 2002) 11971956
Grb2 Embryonic lethality Endoderm (Cheng et al., 1998) 9865697
Grb10 30% larger in size than wildtype Brain, liver (Charalambous et al., 2003) 12829789
Grb14 Glucose tolerance improvement Liver, skeletal muscle (Cooney et al., 2004) 14749734
Hck Normal Macrophages (Lowell et al., 1994)  8125254
Itk Normal T lymphocytes (Liao and Littman, 1995) 8777721
Jak1 Perinatally lethal, nursing defect Neurons, fibroblasts, T and B lymphocytes (Rodig et al., 1998) 9590172
Jak2 Embryonic lethality Hematopoeitic blood cells (Neubauer et al., 1998; Parganas et al., 1998) 9590174, 9590173
Jak3 Immunodeficient; lymphopenia Thymus, spleen, lymph nodes (Nosaka et al., 1995; Thomis et al., 1995) 7481769, 7481767
Lck Thymic atrophy Fetal thymus (Molina et al., 1992)  1579166
Lnk Splenomegaly, defects in hematopoietic lineages Hematopoietic progenitor cells, spleen (Takaki et al., 2000; Velazquez et al., 2002) 11114373, 12070287
Lyn Hyperglobulinemic, Glomerulonephritis  B lymphocytes, mast cells (Hibbs et al., 1995; Nishizumi et al., 1995) 7585947, 7584145
Matk Normal None (Hamaguchi et al., 1996) 8694808
Mist Normal None (Utting et al., 2004) 15199160
Nck1 Normal None (Bladt et al., 2003) 12808099
Nck2 Normal None (Bladt et al., 2003) 12808099
Pik3r1 X-linked immunodeficiency; hypoglycemia B lymphocytes (Fruman et al., 1999; Suzuki et al., 1999) 9888855
Pik3r2 Hypoglycemia Muscle (Ueki et al., 2002) 11752399
Plcg1 Embryonic lethality between E 8.5-9.0 N/A (Ji et al., 1997) 9096335
Plcg2 Viable, B-cell deficiency B lymphocytes (Wang et al., 2000) 10933392
Ptpn6 Immunity and hematopoiesis defects T lymphocytes (Shultz et al., 1993; Van Zant and Shultz, 1989) 8324828, 2783574
Ptpn11 Embryonic lethality at E 10.5   Node, notochord (Arrandale et al., 1996; Saxton et al., 1997) 8702915, 9171349
Rasa1 Embryonic lethality by E 10.5 Vascular system, endothelial cells (Henkemeyer et al., 1995) 7477259
Rin1 Normal Amygdala (Dhaka et al., 2003) 12574403
Sh2b Growth retardation, fertility defect, insulinemia Testis, ovaries, skeletal muscle, liver and fat (Duan et al., 2004; Ohtsuka et al., 2002) 15314154, 11940664
Sh2d1a Recapitulates X-Linked lymphoproliferative disease T and (B) lymphocytes (Crotty et al., 2003; Czar et al., 2001; Wu et al., 2001) 12529646, 11404475, 11323694
Sh2d2a Susceptible to Lupus-like autoimmune disease T lymphocytes (Rajagopal et al., 1999) 10587356
ShbViable and fertile    N/A    (Kriz et al., 2007)17676633 
ShcA Embryonic lethality by E 11.5 Heart (Lai and Pawson, 2000) 10809671
ShcB Normal Sensory neurons (Sakai et al., 2000) 11163269
ShcC Normal None (Sakai et al., 2000) 11163269
Ship Fail to thrive with splenomegaly Spleen, lymphoid, erthryoid, myeloid cells (Helgason et al., 1998) 9620849
Ship2 Severe neonatal hypoglycemia.  Liver (Clement et al., 2001) 11343120
Slap Fertile and healthy T lymphocytes (Sosinowski et al., 2001) 11567635
Slp76 Impaired viability; defective thymocyte development T lymphocytes (Pivniouk et al., 1998) 9695951
Socs1 Fatty degeneration of the liver Liver, Thymocytes (Starr et al., 1998) 9826711
Socs2 Gigantism Most visceral organs (Metcalf et al., 2000) 10890450
Socs3 Embryonic lethality between E 11-13 Placental, blood vessel (Marine et al., 1999; Roberts et al., 2001) 10490101,  11481489
Socs5 Normal None (Brender et al., 2004) 15199163
Socs6 Normal but weigh 10% less than wild-type N/A (Krebs et al., 2002) 12052866
Socs7 Healthy and fertile but die from hydrocephalus Brain (Krebs et al., 2004) 15494444
Src Defective bone remodeling and osteoporosis. Bone osteoclast (Soriano et al., 1991) 1997203
Srms Normal None (Kohmura et al., 1994) 7935409
Stat1 Normal but sensitive to infection T lymphocytes, macrophages (Meraz et al., 1996) 8608597
Stat2 Exhibit multiple defects in immune response Fibroblasts (Park et al., 2000) 11163195
Stat3 Embryonic lethality between E 6.5-7.5 Visceral endoderm, T lymphocytes, (Takeda et al., 1997) 9108058
Stat4 Normal T lymphocytes (Kaplan et al., 1996) 8700209
Stat5a Normal  Mammary glands (Liu et al., 1997) 9009201
Stat5b Decrease growth in males Liver, mammary glands, adipose tissue (Teglund et al., 1998) 9630227
Stat6 Normal T and B lymphocytes (Shimoda et al., 1996) 8602264
Syk Perinatal lethality and blocked B-cell development B lymphocytes (Cheng et al., 1995; Turner et al., 1995) 7477353, 7477352
Tec Normal   B lymphocytes (Ellmeier et al., 2000) 11104803
Tns Normal Kidney, muscle myoblast (Lo et al., 1997) 9087448
Txk Death by 102 days Splenocytes (Schaeffer et al., 1999) 9891083
Tyk2 Normal T lymphocytes (Karaghiosoff et al., 2000; Shimoda et al., 2000) 11070173, 11070174
Vav1 Normal T lymphocytes (Zhang et al., 1994) 7809116
Vav2 Normal None (Tedford et al., 2001) 11376343
Vav3 Normal None (Fujikawa et al., 2003) 14623913
Yes Normal None (Stein et al., 1994) 7958873
Zap70 SCID T lymphocytes (Negishi et al., 1995) 7630421

Comments