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Transgenic and Knockout Mouse - Activities

Objectives

  • to develop migration related conditional knockout mice and RNAi knock-downs
  • to generate knock-ins of mutant and tagged molecules
  • to derive cell lines and develop vectors

Collaboration and Release Policy

Mice in Development by the CMC | Other Migration-related Mice & Cell Lines

Mice in Development by the CMC

Gene Target Method Status Phenotype Contact (Collaborators)
Enah, Vasp, Evl Mena, VASP, Evl triple null ES cell lines Lines available Completed - Kwiatkowski et al., 2007, Dent et al., 2007 Frank Gertler
Evl Evl-flox Targeted - floxed Mouse available Completed - Kwiatkowski et al., 2007 Frank Gertler
Evl Evl Targeted - nonfloxed Mouse available Completed - Kwiatkowski et al., 2007 Frank Gertler
Git2 GIT2 Gene Trap (Bay Genomics) Mouse available Completed - Mazaki et al., 2006 Rick Horwitz
Itgb3 Beta-3 integrin Y747A Targeted - knockin Mouse available Completed - Petrich et al., 2007, Reviewed Mark Ginsberg
Itgb3 Beta-3 integrin L746A Targeted - knockin Mouse available Completed - Petrich et al., 2007, Reviewed Mark Ginsberg
Txnip Txnip Targeted - floxed Mouse available Completed - Yoshioka et al., 2007 Burds(R. Lee)
Cfl1 Cofilin 1 Targeted - floxed Mouse generated Completed - evaluation in process Burds(J. Condeelis)
Coro1c Coronin 1C Gene Trap (Bay Genomics) Mouse generated Completed - evaluation in process Burds(J. Bear) / Bay Genomics
Dock1 DOCK 180 Targeted -nonfloxed Mouse generated Completed - evaluation in process Burds(J.-F. Cote)
Dock1 DOCK 180 Targeted - floxed Mouse generated Completed - evaluation in process Burds(J.-F. Cote)
Enah mEna Targeted - floxed Mouse generated Completed - evaluation in process Frank Gertler
Itga4 Alpha-4 integrin Ser1021Ala Targeted - floxed Mouse generated Completed - evaluation in process Mark Ginsberg
Itga5 Alpha-5 integrin Targeted - floxed Mouse generated Completed - evaluation in process Richard Hynes
Layn Layilin Targeted - nonfloxed Mouse generated Completed - evaluation in process Richard Hynes
Layn Layilin Targeted - floxed Mouse generated Completed - evaluation in process Richard Hynes
Raph1 Lamellipodin Targeted - floxed Mouse generated Completed - Incomplete KO Frank Gertler
RIAM RIAM Targeted - floxed Mouse generated Completed - evaluation in process Frank Gertler
Srf SRF - activated Targeted at ROSA26 Mouse generated Completed - evaluation in process Frank Gertler
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Other Migration-related Mice

JAX icon = Link to the JAX database

Gene Target Description Mouse Phenotype Publication
Abl1 Abl   Defect in spermatogenesis Kharbanda et al. 1998
Abl1 Abl   Perinatal mortality, runtedness, and abnormal spleen, thymus, head, and eye development Schwartzberg et al. 1991; Tybulewicz et al. 1991
Abl1 Abl   Abl-/- mice that survive to adulthood have low levels of mature B and T cells Hardin et al. 1995
Abl1/Abl2 Abl/Arg double Abl/Arg double Die E11 - neurulation defects Koleske et al. 1998
Akt1 icon linking to JAX database AKT (PKB) Akt1/PKBalpha Partial lethality between E13.5 and 3 weeks after birth. Surviving adults are fertile, but show 20% weight reduction. No effect seen on glucose metabolism Cho H et al. 2001
Akt2 AKT (PKB) Akt2/PKBbeta Reduction of insulin-stimulated glucose uptake in muscle and fat and reduction in whole body glucose disposal Cho H et al. 2001
Actn3 Alpha-actinin alpha-actinin-3 In progress - Institute for Neuromuscular Research, Children's Hospital at Westmead (Australia) Link
Itga4 icon linking to JAX database alpha4 integrin    
Itga4 alpha4 integrin Ser1021 Ala CMC Target
Itga4 alpha4 integrin Ser1021 Glu  
Itga5 icon linking to JAX database alpha5 integrin   CMC Target
Rapgef1 C3G   Death before E7.5 Ohba et al. 2001
Rapgef1 C3G hypomorph Death at E11.5 due to haemorrhage and vascular integrity defects Voss AK et al. 2003
Capn1 Calpain I (mu-calpain) (Capn1)   Viable and fertile. Reduced platelet aggregation and reduced tyrosine phosphorylation of the beta3 subunit of alphaIIbbeta3 integrin Azam M et al. 2001
Capn2 Calpain II (m-calpain) (Capn2)   None, though elimination of the Capn4 gene (see below) destroys the CalpainII complex. Arthur JS et al. 2000
Capns1 Calpain IV (Capn4)   Embryonic lethality at mid-gestation with defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors Arthur JS et al. 2000
Capzb CapZ    
Bcar1 CAS (p130)   Embryonic lethality showing systemic congestion and growth retardation. Honda et al. 1998
Cask CASK insertional mutant X-linked gene, all males show cleft palate and die within 24 hours of birth. Viable females did not display cleft palate, but had smaller heads than wt littermates, showed spinal kinks epidermal hyperplasia, were 50% the weight of littermates, failed to thrive and rarely produced any litters. Laverty HG and Wilson JB 1998
Cav1 Caveolin-1   Heart defects due to myocyte hypertropy with interstitial/perivascular fibrosis. Also shows hyperactivation of the Ras-p42/44 MAP kinase cascade Cohen et al. 2003
Cav1 Caveolin-1   Cardiovascular defects due to lack of nitric-oxide and Calcuim signaling, and hyperproliferation of lung endothelial cells Drab M et al 2001; Razani B et al 2001
Cav1 Caveolin-1   Dramatic increase in the incidence of urinary calcium stone formation Cao G et al. 2003
Cav1 Caveolin-1   Null mice are unresponsive to insulin due to drastic reduction in insulin receptor protein levels (> 90%). IR-mRNA levels are normal, suggesting caveolin-1 is necessary for insulin receptor stabilization. Cohen AW et al 2003
Cblb Cbl Cbl-b Viable and grossly normal Chiang YJ et al 2000
Cblc Cbl Cbl-c Viable, fertile, grossly normal. increased number of T-cell receptor B expressing cells, lymphoid hyperplasia, and primary splenic extramedullary hemopoiesis Murphy MA et al 1998
Cfl1 Cofilin   CMC Target
Coro1c Coronin   CMC Target
Crk, Crk7 Crk   Elimination of Crk-II resulted in no obvious abnormalities Imaizumi et al. 1999
Csk icon linking to JAX database Csk   Neural tube defects, Death between E9 and E10 Imamoto & Soriano, 1993
Csk icon linking to JAX database Csk   Developmental arrest in the 10-12 somite stage, increase in p60c-src, p59fyn and p53/p56lyn kinase activity Nada et al. 1993
Mcf2 Dbl   Viable, fertile, grossly normal. correct disposition of the major neural structures and normal cortical stratification. However, in distinct populations of cortical pyramidal neurons, the length of dendrites was significantly reduced Hirsch E et al. 2002
Dock1 DOCK 180   CMC Target
Fhl2 DRAL (FHL2)   Viable, grossly normal. Null animals have an exaggerated hypertrophic response to beta-adrenergic stimulation. Kong Y et al. 2001
Fhl2 DRAL (FHL2)   Viable, grossly normal. Normal cardiac development, and no increase in FHL1 or FHL3 mRNA Chu PH et al. 2000
Enah ENA (see mena)   (see mena)
Rdx ERM (ezrin/radixin/moesin) radixin (Rdx) Normal at birth, but increased levels of conjugated bilirubin at week 4 results in mild liver injury after 8 weeks. Kikuchi S et al. 2002
Msn ERM (ezrin/radixin/moesin) moesin (Msn) (X-linked gene) Viable, fertile. No change in ezrin or radixin levels Doi Y et al. 1999
Evl Evl   CMC Target
Ptk2 Fak   Death at E8.5 with impaired blood vessel development Ilic et al. 2003
Gsn Gelsolin (or ADF)   Gelsolin deficiency was associated with normal skeletal development and endochondral bone growth, but mildly abnormal epiphyseal structure, retained cartilage proteoglycans in metaphyseal trabeculae, and increased trabecular thickness. With age, gelsolin-deficient mice expressed increased trabecular and cortical bone thickness producing mechanically stronger bones. Chellaiah M et al., 2000
Git2 GIT2 Null Alive, fertile, with some splenomegaly and immunodeficiency. Decreased neutrophil polarization and chemotaxis.Mazaki et al. 2006
Grb2 Grb2 hypomorph Perinatal death due to cleft palate Saxton TM et al. 2001
Grb2 Grb2   Embryonic lethality at E4. failure in endoderm differentiation. Chimeric embryos show that Grb2-null cells do not contribute to the epiblast. Cheng AM et al. 1998; Saxton TM et al. 2001
  Integrins Review See Review for information on 22 different integrin Kos Hynes, 2002, Cell v110
Insr icon linking to JAX database, icon linking to JAX database IR   Severe insulin resistance and death from ketoacidosis within 3–7 days after birth Accili D et al. 1996
Insr icon linking to JAX database, icon linking to JAX database IR Conditional in pancreatic beta cells only Viable, fertile. Normal blood glucose levels, but loss of insulin secretion in response to glucose, and progressive glucose intolerance. Kulkarni RN et al. 1999
Irs1 IRS-1   Viable, but neonates are half the size of littermates, show impaired glucose tolerance Araki et al. 1994
Irs1 IRS-1   Postnatal growth was also retarded, and were resistant to insulin, IGF-1 and IGF-2 Tamemoto et al. 1994
Irs1, Irs3 icon linking to JAX database IRS-1/3 Irs1/Irs3 double Early-onset severe lipoatrophy associated with marked hyperglycemia, hyperinsulinemia, and insulin resistance. Laustsen PG et al. 2002
Ptprf LAR-PTP   Viable, but LAR-/- females have mammary gland defects and cannot nurse the pups Schaapveld et al. 1997
Ptprf LAR-PTP   Reduced numbers of cholinergic cells Van Lieshout et al. 2001
Ptprf LAR-PTP   Reduced levels of plasma insulin and glucose, 47% reduction in insulin-stimulated PI3-kinase activity Ren et al. 1998
Layilin Layilin   CMC Target
Stk10 LOK (lymphocyte-oriented kinase)   Leukocyte-function-associated aggregation of mitogen-stimulated T cells was greatly enhanced in LOK-deficient mice. Endo et al., 2000
Enah Mena   Viable, with misrouted axons, failed decussation of the corpus callosum, and defects in both the hippocampal commissure and the pontocerebellar pathway Lanier et al. 1999
Myh2 Myosin heavy chain II-A   Defects in cell adhesion and visceral endoderm. Conti et al., 2004
Myh10 Nonmuscle myosin II-B   Required for normal development of mouse heart. Tullio et al., 1997
Myh6 Cardiac alpha myosin, heavy chain   Dosage effects and functional deficits in the heart. PMID(Jones et al., 1996|8878443
Nck1, Nck2 Nck1 & Nck2   Nck genes have broad and overlapping expression pattern and mice deficient in either Nck1 or Nck2 are viable, whereas inactivation of both resulted in profound defects in mesoderm-derived notochord and embryonic lethality at day 9.5 Bladt et al., 2003
Pxn Paxillin   Embryonic lethality due to abnormal development of mesodermally derived structures such as the heart and somites Hagel et al. 2002
Hspg2 Perlecan   Perlecan-null mice show severe defects of skeletal developmental and die at mid-gestation of heart failure. Surviving embryos exhibit severe chondrodysplasia between E15 and birth, with short limbs, neck and snout. They have cleft palates and die shortly after birth from respiratory failure. Costell et al., 1999
Pik3cd PI 3-K p100 subunit Viable, with decreased numbers of mature b cells, a block in pro-B-cell differentiation, and a B1 B-cell deficiency. Decreased immunoglobulin levels. Elimination of response to T-cell-dependent antigens, and reduction in response to T-cell-independent antigens. Jou et al. 2002
Pik3cd PI 3-K Review Review of PI3k family and signaling component mouse knockouts Katso et al. 2001
Prkce icon linking to JAX database PKC PKC-epsilon Viable, grossly normal. Decreased epinephrine-induced and acetic acid–associated hyperalgesia Khasar SG et al. 1999
Prkce icon linking to JAX database PKC   Reduced ethanol withdrawal severity Olive MF et al. 2001
Prkce icon linking to JAX database PKC   Decreased anxiety-like behavior, reduced levels of stress hormones Hodge CW et al. 2002
Prkce icon linking to JAX database PKC   Decreased hypoxic pulmonary vasoconstriction Littler CM et al. 2003
Prkcc icon linking to JAX database PKC PKC-gamma Viable, diminished long-term potentiation of synaptic transmission in the hippocampus and mild defects in spatial and contextual learning. Abeliovich A et al. 1993; Abeliovich A et al. 1993
Prkch PKC PKCeta In Progress -University of Tokyo see Kashiwagi et al. 2002
Plcg1 PLC-gamma (Plcg1)   Embryonic lethal. Embryos appear normal at E8.5, but do not develop past E9.0 Ji Q, Winner GE et al. 1997
Pkd1 Polycystin-1 (Pkd1) Truncation mutation del34 Embryonic lethality at E15.5-birth with enlarged, cystic kidneys, pancreatic ductal cysts and pulmonary hypoplasia Lu W, Peissel B et al. 1997
Pkd1 Polycystin-1 (Pkd1) Truncation del43/45 Embryonic lethality at E10.5- E15.5 due to edema, focal vascular leaks and hemorrhage Kim K and Drummond I 2000
Pkd1 Polycystin-1 (Pkd1) knockout Death from E13.5-birth with polyhydramnios, systemic edema, polycystic kidney and pancreatic disease, and spina bifida occulta and osteochondrodysplasia Lu W et al. 2001
Pkd2 Polycystin-2 (Pkd2)   Embryonic lethality after E13.5, Adult Pkd2+/- mice have reduced survival. Animals with point-mutant/over/null genotypes develop renal failure and early death (13 months) Wu G et al 2000
Pkd2 Polycystin-2 (Pkd2)   Embryos show right pulmonary isomerism, randomization of embryonic turning, heart looping, and abdominal situs Pennekamp P et al 2002
Pfn1 Profilin Profilin I Very early embryonic lethality - no viable Knockout blastocysts found. Heterozygotes show reduced embryonic survival Witke et al. 2001
Pfn2 Profilin Profilin II Neurons show intact actin cytoskeleton, but have altered kinetics of synapse recycling. Mice are anxious, do not react to stress, and lack maternal behaviors Witke Group EMBL 201 Research Reports
Pten icon linking to JAX database PTEN   Homozygotes show early embryonic lethality, Pten+/- mice show hyperplastic-dysplastic changes in the prostate, skin abd colon as well as spontaneous development of germ cell, gonadostromal, thyroid and colon tumors. DiCristofano et al 1998
Pten icon linking to JAX database PTEN   Hets show breast tumors, endometrial hyperplasia, endometiral cancer, hamartoamous tumors of the GI tract, and both prostate and adrenal neoplasias. Most tumors show LOH at Pten. Stambolic et al. 2000
Pten icon linking to JAX database PTEN keratinocyte-specific Within 3 weeks of birth, 90% of k5Pten(flox/flox) mice die of malnutrition. Surviving mice develop spontaneous tumors within 8.5 months of birth. Pups display epidermal hyperplasia and hyperkeratosis, leading to wrinkled skin as well as ruffled, shaggy, and curly hair. Suzuki et al. 2003
Ptpn1 PTP1B Null Low body weight due largely to a dramatic reduction in body fat content and hypermetabolism Klaman LD et al 2000
Ptpn1 PTP1B del5/6 Viable, increased insulin sensitivity, failed to gain weight when maintained on a high-fat diet Elchebly M et al. 1999
Ptk2b PYK2   Viable, with suppression of IgM, IgG3 and IgG2a production Guinamard et al 2000
Rac2 icon linking to JAX database Rac2 null Mice show baseline neutrophilia, reduced inflammatory peritoneal exudate formation and increased mortality when challenged with Aspergillus fumigatus. Roberts AW et al. 1999
  Rho C3 transgenic mice (thymic targeting of transgene abolishing biological function of Rho) Maturational, proliferative and cell survival defects during T-cell development were observed, that severely impair the generation of normal numbers of thymocytes and mature peripheral T cells. Henning SW. et al., 1997
Rock2 ROCK-II   90% embryonic lethal 13.5 days postcoitum due to placental abnormalities Thumkeo et al., 2003
Shc1 Shc p52ShcA Embryonic lethal at E11.5 due to cardiovascular defects Lai KM and Pawson T 2000
Ptpn11 SHP-2 (ptpn11 gene) Shp2/EGFR double Premature lethality with aortic stenosis and regurgitation. Chen et al 2000
Ptpns1 SHPS-1 truncation del7/8 Viable, fertile, mild thrombocytopenia, abnormal distribution of B lymphocytes and megakaryocytes in spleen Inagaki K et al. 2000
Ptpns1 SHPS-1 truncation del7/8 Platelets were cleared from the bloodstream more rapidly, peritoneal macrophages from the mutant mice phagocytosed red blood cells more effectively , and null mice exhibited an increase both in the rate of cell spreading and in the formation of filopodia-like structures at the cell periphery. Yamao T et al. 2002
Src icon linking to JAX database, icon linking to JAX database Src or Src1 Src (p60-Src) Src -/- mice exhibit osteopetrosis owing to the inability of osteoclasts to form a sealing zone. Lowe C, et al., 1993
Src icon linking to JAX database, icon linking to JAX database SrcFK Src1 Src1-/- mice exhibit moderate motor dysfunction, but normal hippocampal function. Delay in purkinje cell maturation at eh neonatal stage Nishihara et al. 2003
Srf Srf (activated)   CMC Target
Sdc4 Syndecan-4   Viable, fertile, grossly normal. delay in wound healing Ishiguro K et al 2000; Echtermeyer F et al. 2001
Tln1 Talin 1   Embryonic lethality at E8.5-9.5 with disorganization of embryos at gastrulation. Monkley et al 2000
Tns Tensin   Viable and healthy at birth: weakness, renal failure and cysts in proximal kidney tubules later in life. Analysis of cysts show disruptions in cell matrix junctions and weakening of focal adhesion Lo et al. 1997
Tns Tensin   Delayed regeneration of wounded skeletal muscle in Tensin-/- mice, correlates with delayed expression of myosin, paxillin and dystrophin. Ishii and Lo, 2001
Trio Trio   Embryonic lethality between E15.5 and birth. Abnormal skeletal myofibers and aberrant organization in the hippocampus and olfactory bulb. O'Brien SP et al 2000
Txnip Txnip   Viable, altered cardiac response to pressure overload. Deletion of Txnip plays an unanticipated role in myocardial energy homeostasis rather than redox regulation. Yoshioka et al 2007
Plau icon linking to JAX database, icon linking to JAX database, icon linking to JAX database, icon linking to JAX database uPA   Greatly impaired in inflammatory cell recruitment, migration defect in wounded smooth muscle lack of melanomas after chemical induction of melanocytic neoplasms suggests that uPA contributes to malignant progression Shapiro et al. 1996
Plau icon linking to JAX database, icon linking to JAX database, icon linking to JAX database, icon linking to JAX database uPAR (CD87)   u-PAR deficiency Is not lethal and did not affect wound healing as assayed by: arterial neointima formation, neointimal cell accumulation, or migration of smooth muscle cells. Carmeliet et al. 1998
Plau icon linking to JAX database, icon linking to JAX database, icon linking to JAX database, icon linking to JAX database uPAR (CD87)   Adult mice are anxious, exhibit spontaneous seizure activity and have higher susceptibility to pharmacologically induced convulsions: decrease in GABA-immunoreactive interneurons Powell et al. 2003
Plau icon linking to JAX database, icon linking to JAX database, icon linking to JAX database, icon linking to JAX database uPAR (CD87)   Reduced platelet survival, but the 2-3fold increase in number of megakaryocyes in marrow and spleen results in increased platelet production to compensate Piguet et al. 2000
Plau icon linking to JAX database, icon linking to JAX database, icon linking to JAX database, icon linking to JAX database uPAR (CD87)   Reduction of recruitment of leukocytes to inflamed or infected areas May et al. 1998; Gyetko et al. 2000
Plau icon linking to JAX database, icon linking to JAX database, icon linking to JAX database, icon linking to JAX database uPAR (CD87)   Delay in mortality following infection with severe malaria Piguet et al. 2000
Vasp VASP   Significant reduction in cAMP- and cGMP-mediated inhibition of platelet aggregation Aszódi A et al. 1999
Vasp VASP   Hyperplasia of megakaryocytes in bone marrow and spleen, but no other macroscopic or microscopic abnormalities Hauser W et al 1999
Vasp, Enah VASP/Ena Ena/VASP double Embryonic Lethal Gertler Lab, unpublished data
Enah, Vasp, Evl Ena/VASP/Evl Ena/VASP/Evl triple chimera Neuronal ectopias, altered intralayer positioning in the cortical plate, and no axon fiber tract formation during corticogenesis. Kwiatkowski et al 2007
Vasp VASP protein sequestering Aberrant placement of early-born pyramidal neurons in the superficial layers of both the embryonic and the postnatal cortex in a cell-autonomous fashion. Goh KL et al 2002
  Vav null Mice are viable and display profound defect in the positive selection of both class I- and II-restricted T cells and while negative selection is not abolished it is much less effective in the absence of Vav. Turner M et al. 1997
  Vav null Mutant mice have normal antibody responses to haptenated Ficoll, but show defective class switching to IgG and germinal center formation when immunized with haptenated protein. Gulbranson-Judge A et al. 1999
Vav1, Vav2, Vav3 Vav 1/2/3 deficient Mice lacking all Vav family proteins and show that Vav-null mice produce no functional T or B cells and completely fail to mount both T-dependent and T-independent humoral responses Fujikawa K. et al., 2003
Vim Vimentin   No obvious phenotype Colucci-Guyon E et al 1994
Vim Vimentin   Significant attenuation of flow-induced dilation of mesenteric resistance arteries perfused in vitro Henrion D et al 1997
Vcl Vinculin   Death by E10, with embryos displaying 30-40% reduction in size, lack of midline fusion of the rostral neural tube and developmental defects in heart, somites and limbs. Xu et al. 1998
Zyx Zyxin   Viable, fertile, no obvious histological abnormalities in any of the organs examined. Hoffman LM et al 2003
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Other Migration-related Cell Lines

JAX icon = Link to the JAX database

Gene Target Description Mouse Phenotype Publication
Abl1, Abl2 Abl/Arg double neuroepithelial Alterations in actin cytoskeleton Koleske et al. 1998
Rapgef1 C3G embryonic fibroblasts Impaired cell adhesion, delayed cell spreading and accelerated cell migration Ohba Y et al 2001
Rapgef1 C3G hypomorph in MEFs Abnormal response to PDGF-BB, cell adhesion defects and lacked paxillin and integrin-beta1-positive cell adhesions. Integrin-beta3-positive cell adhesions formed normally. Voss AK et al. 2003
Capns1 Calpain IV (Capn4) fibroblasts Decreased migration rates, abnormal organization of actin cytoskeleton, loss of central stress fibers, and decreased numbers of focal adhesions. No proteolysis of talin Dourdin et al. 2001
Bcar1 CAS (p130) embryonic fibroblasts Impaired formation of actin stress fibers, reduced cell spreading, cell migration, and transformation by activated Src Honda et al 1998
Cbl, Cblb Cbl c-Cbl Cbl-b double knock-out T cells Hyper responsive upon anti-CD3 stimulation because the cells could not down-modulate surface TCR after ligand engagement Naramura M et al 2002
Parva CH-ILKBP siRNA in HeLa cells 40% of cells underwent apoptosis 48 hours after siRNA transfection. Loss of membrane translocation of PKB/Akt Fukuda T et al. 2003
Csk Csk embryonic fibroblasts Elimination of G-protein-induced actin stress fibers Lowry et al. 2002
Enah Ena see VASP  
Ptk2 FAK embryonic fibroblasts Reduced migration rate and an increase in the number and size of peripherally localized adhesions Ilic D. et al. 1995
Ptk2 FAK   Elevated levels of Pyk2 Sieg DJ et al 1998
Ptk2, Bcar1 FAK, Cas double embryonic fibroblasts Defects in ephrinA1-induced cell spreading Carter et al. 2002
Gsn Gelsolin osteoclasts Gelsolin deficiency blocks podosome assembly and alpha(v) beta(3) integrin-stimulated signaling, resulting in hypomotile osteoclasts due to the retarded remodeling of the actin cytoskeleton. Chellaiah M et al., 2000
Irs1 IRS-1 primary beta islet cells Insulin secretory defects in response to glucose and arginine, and 2-fold reduction in insulin expression Kulkarni RN et al. 1999
Map3k1 MEKK1 fibroblasts Loss of vinculin in focal adhesions of migrating cells, increased cell adhesion and impeded rear-end detachment Cuevas et al., 2003
Nck1, Nck2 Nck1 &Nck2 embryonic fibroblasts Defects in cell motility and organization of the lamellipodial actin network Bladt et al., 2003.
Pxn Paxillin cultured ES cells Delayed spreading on fibronectin and laminin, reduced tyrosine phosphorylation of Fak Wade et al. 2002
Pxn Paxillin fibroblasts Abnormal focal adhesions, reduced cell migration, inefficient localization of Fak), defects in cortical cytoskeleton and cell spreading on fibronectin. Hagel et al. 2002
Pik3cd PI 3-K p85alpha KO polymorphonuclear leukocytes Normal cellular motility in the presence of granulocyte macrophage-colony stimulating factor Yasui et al 2002
Plcg1 PLC-gamma (Plcg1) MEFs Studied PDGF effects - found normal increase in plasma membrane ruffles following PDGF addition. Hess JA et al. 1998
Plcg1 PLC-gamma (Plcg1) MEFs Null cells show decreased spreading and therefore grow to a higher saturation density, Ji QS et al. 1998
Plcg1 PLC-gamma (Plcg1) MEFs Insulin-like growth factor cannot rescue Plcg1-null cells from suspension-induced cell death Chattopadhyay A and Carpenter G 2002
Pten PTEN ES cells Pten -/- ES cells show an enhanced ability to generate tumors in nude and synergistic mice and differentiate aberrantly in culture. DiCristofano et al 1998
Pten PTEN ES cells and MEFs Accelerated transition from the G(2)/M to the G(1) phase of the cell cycle Kandel ES et al. 2002
Pten PTEN PCT and NIH3T3 fibroblasts Loss of Pten leads to increased AKT activity Choi Y et al. 2002
Ptpn1 PTPalpha immortalized embryonic fibroblasts Altered cell shape and reduced focal adhesion kinase (Fak Tyr397) phosphorylation Zeng et al., 2003
Ptpn1 PTP1B embryonic fibroblasts (transformed) Enhanced plating efficiency and IGF-I-mediated motility, enhanced IGF-I-mediated protection from apoptosis Buckley DA et al 2002
Ptprf PTP1B embryonic fibroblasts (transformed) Delay in cell spreading Cheng A et al 2001
Ptpn12 PTP-PEST fibroblasts Increased rate of spreading on fibronectin. Increase in the number and size of vinculin containing focal adhesions. Angers-Loustau A et al. 1999
Ptpn12 PTP-PEST fibroblasts 2.6-fold increase in phosphorylation of endogenous c-Abl, with prolonged Abl-activation (at least 60 minutes, as compared to less than 30 min for wt cells) Cong F et al. 2000
Rac2 Rac2 neutrophils Neutrophils display significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1 and in both F-actin generation and p38 and unexpected p42/p44 MAP kinase activation induced by chemoattractants. Superoxide production by bone marrow neutrophils was also significantly reduced Roberts AW et al., 1999
Rac2 Rac2 T cells Proliferation was reduced in Rac2(-/-) T cells upon stimulation with either plate-bound anti-CD3 or T cell receptor-specific antigen and was accompanied by decreased activation of mitogen activated protein kinase extracellular signal-regulated kinase (ERK) 1/2 and p38 as well as reduced Ca (2)+ mobilization. TCR stimulation-induced actin polymerization was reduced and there were significant phenotypic similarities with Vav (-/-) cells implication Rac2 as a downstream mediator of Vav signaling. Yu H et al. 2001
Ptpns1 SHPS-1 fibroblasts with truncation del 7/8 Increased rate of spreading on fibronectin, but defective in subsequent polarized extension and migration. Inagaki K et al. 2000
Sdc4 Syndecan-4 fibroblasts reduced phosphorylation of Fak Tyr(397) Wilcox-Adelman SA et al. 2002
Sdc4 Syndecan-4 fibroblasts Normal formation of focal adhesions on fibronectin Ishiguro K et al. 2000
Tln1 Talin trophoblast cells Reduced spreading on fibronectin and laminin. Monkley et al 2000
Plau uPAR embryonic fibroblasts LRP-independent reduction of Rac1 activation Ma et al. 2002
Vasp VASP fibroblasts Very spread - covering twice the substrate surface area as compared to wild type. Normal Mena and Evl levels. Increased activation of PAK pathway. Garcia Arguinzonis MI et al. 2002
Vasp, Enah VASP/Ena Ena/VASP double Review - Bear JB et al. 2001
Enah, Vasp, Evl Ena/VASP/Evl Ena/VASP/Evl triple neurons Neuritogenesis in Ena/VASP-null neurons can be rescued by restoring filopodia formation through addition of laminin or expression of actin nucleating protein mDia2. Dent EW et al 2007
Vav1 Vav1 thymocytes Thymocytes are less efficient at forming conjugates with antigen presenting cells presenting agonist peptide than wild-type cells and this may be related to loss of TCR-induced activation of the integrin LFA-1 associated with these cells. Ardouin et al. 2003
Vcl Vinculin F9 embryonal carcinoma cells Normal adherence to fibronectin, reduced spreading, increased amounts of alpha-actinin, talin and paxillin at focal adhesions Volberg et al. 1995
Vcl Vinculin F9 embryonal carcinoma cells Altered cell morphology and motility. absence of stress fibers Goldmann et al. 1995
Vcl Vinculin embryonic fibroblasts Reduced adhesion to fibronectin, vitronectin, laminin and collagen and increased migration rates over these substrates Xu et al. 1998
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