PhysGen Knockouts

DEADLINE EXTENDED!  Nominate genes for modification before May 18th, 2012:
We need your input and to make sure everyone has a chance to respond, we've extended the submission deadline!  We are putting in a resource grant (NHLBI R24) to fund the creation of a community resource of genetically modified rat models using zinc finger nucleases.  Please complete the gene nomination form to let us know what rat strain or series of rat strains would be useful for your area of research.  To be included in the grant application, please return this form no later than May 18, 2012.

 

The PhysGen Knockout program ("Mechanistic Characterization of Genes for Hypertension and Renal Disease") aims to knock out a large number of genes nominated by genome wide association studies, combine these gene knockouts (KO) with hypertensive and normotensive strains, and phenotypically characterize them.

We invite the scientific community to nominate genes involved in the development of hypertension and renal disease. To do so, please contact Mindy Dwinell, Ph.D. (mrdwinel@mcw.edu).   

Key Personnel   Role  Contact email
Howard Jacob, Ph.D.  Principal Investigator  jacob@mcw.edu 
Allen Cowley, Jr., Ph.D.  Co-Investigator  cowley@mcw.edu
Melinda Dwinell, Ph.D. Co-Investigator  mrdwinel@mcw.edu  
Aron Geurts, Ph.D.  Co-Investigator  ageurts@mcw.edu 
Andrew Greene, Ph.D.  Co-Investigator  agreene@mcw.edu 
Jozef Lazar, MD, Ph.D.  Co-Investigator  jlazar@mcw.edu 
Julian Lombard, Ph.D.  Co-Investigator  jlombard@mcw.edu 
David Mattson, Ph.D.  Co-Investigator  dmattson@mcw.edu 
Carol Moreno Quinn, MD, Ph.D.  Co-Investigator  quinn@mcw.edu 

Genome view of PhysGen Knockout genes targeted using zinc finger nucleases.  Each targeted gene is represented by a blue bar.  Click on any bar to see a more detailed view. 

Strain Development Progress

Gene 

Symbol 

Allele 

 Strain

Received 

Injected

 Hit 

 Backcrossing  Intercrossing  In Phenoytping  Data available in PhenoMiner  Strain available for distribution Strain cryopreserved 

Apolipoprotein E 

 Apoe

Apoeem7Mcwi

 SS-Apoeem7Mcwi

Yes

Yes

Yes

Yes 

 Yes

 Yes

   Yes  
Apoe Apoeem8Mcwi SS-Apoeem8Mcwi Yes Yes Yes Yes Yes Yes Yes

cytochrome P450, family 4, subfamily A, polypeptide 2 

 Cyp4a2 Cyp4a2em1Mcwi

Yes

Yes

 Yes 

Yes 

  Yes  Yes   Yes  
cytochrome P450, family 4, subfamily a, polypeptide 3 Cyp4a3 Cyp4a3em3Mcwi Yes Yes Yes Yes Yes Yes Yes

 regulated endocrine-specific protein 18

Resp18

Resp18em2mcwi

Yes

Yes

Yes

  Yes  Yes        
Resp18 Resp18em3Mcwi Yes Yes Yes Yes Yes

 v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)

 Ets1

Ets1em1Mcwi

 SS-Ets1em1Mcwi

Yes

Yes

  Yes

 Yes

 Yes

 Yes

     Yes

nuclear receptor subfamily 2, group F, member 2

Nr2f2

Nr2f2em1Mcwi

Yes

Yes

 Yes  Yes  Yes     Yes  

uromodulin 

 Umod

Umodem1Mcwi

Yes

Yes

  Yes  Yes          

 low density lipoprotein receptor

 Ldlr

Ldlrem1Mcwi

 SS-Ldlrem1Mcwi

Yes

Yes

  Yes

Yes 

 Yes

     Yes  
Ldlr Ldlrem2Mcwi SS-Ldlrem2Mcwi Yes Yes Yes Yes Yes
Ldlr Ldlrem3Mcwi SS-Ldlrem3Mcwi Yes Yes Yes Yes Yes
Ldlr Ldlrem4Mcwi SS-Ldlrem4Mcwi Yes Yes Yes Yes Yes

SH2B adaptor protein 3 

 Sh2b3

Sh2b3em1Mcwi

 SS-Sh2b3em1Mcwi

Yes

Yes

 Yes

Yes 

 Yes

 Yes

 Yes Yes  
Sh2b3 Sh2b3em2Mcwi SS-Sh2b3em2Mcwi Yes Yes Yes Yes Yes Yes Yes

 MAS1 oncogene

 Mas1

Mas1em1Mcwi

 SS-Mas1em1Mcwi

Yes

Yes

 Yes

Yes 

Yes

 Yes

   Yes  

Agouti signaling protein

Asip

Asipem1Mcwi 

 ACI.FHH-(D1Mit18-D1Rat90)(D14Mit11-D14Rat33)(D14Rat65-D14Rat90)/EurMcwi-Asipem1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

 

Yes 

 

sortilin-related VPS10 domain containing receptor 1 

Sorcs1 

Sorcs1em1Mcwi 

 FHH-Chr 1BN-Sorcs1em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

 

Yes 

 

interleukin 1 receptor 1 

Il1r1 

Yes

Yes

 Yes

Yes 

 Yes

 

 

 

 

recombinant activating gene 1 

Rag1 

Rag1em1Mcwi 

 SS-Rag1em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

 

Yes 

 
Rag1 Rag1em2Mcwi SS-Rag1em2Mcwi Yes Yes Yes Yes Yes Yes

sortilin-related VPS10 domain containing receptor 3 

Sorcs3 

Sorcs3em1Mcwi

Yes

Yes

Yes

Yes 

Yes 

 Yes

 

 

 

Nck-associated protein 5 

Nckap5 

Nckap5em1Mcwi 

 SS-Nckap5em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

 

Yes

 
Nckap5 Nckap5em2Mcwi SS-Nckap5em2Mcwi Yes Yes Yes Yes Yes
Nckap5 Nckap5em3Mcwi SS-Nckap5em3Mcwi Yes Yes Yes Yes Yes

Associated Ras oncogene family member (Rab38) 

Rab38 

Rab38em1Mcwi 

 FHH.BN-Rab38em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

 

 Yes

 

Renin 

Ren 

Renem1Mcwi

 SS-Renem1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

 

Yes 

 

natriuretic peptide precursor A

Nppa 

Nppaem4Mcwi

 SS-Nppaem4Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

Yes 

Yes 

 
acyl-CoA dehydrogenase family, member 10 Acad10 Acad10em2Mcwi SS-Acad10em2Mcwi Yes Yes Yes Yes Yes Yes Yes

angiotensin II receptor-associated protein 

Agtrap 

Agtrapem4Mcwi

 SS-Agtrapem4Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

Yes 

 Yes

Yes 
Agrap Agtrapem8Mcwi SS-Agtrapem8Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

leptin 

Lep 

 

Yes

Yes

Yes

 Yes

 

 

 

 

 

potassium inwardly rectifying channel, subfamily J, member 11 

Kcnj11 

Yes

Yes

Yes

Yes

 Yes

 

 

 

 

natriuretic peptide precursor B 

Nppb 

Nppbem2Mcwi 

 SS-Nppbem2Mcwi

Yes

Yes

Yes

Yes 

Yes 

Yes

Yes 

 Yes

 
Nppb Nppbem4Mcwi SS-Nppbem4Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

aldehyde dehydrogenase 2 family (mitochondrial) 

Aldh2 

Aldh2em2Mcwi 

 SS-Aldh2em2Mcwi

Yes

Yes

Yes

Yes 

Yes 

Yes 

Yes

 

 

peroxisome proliferator-activated receptor gamma

Pparg 

Yes

Yes

Yes

Yes

 Yes

 

 

 

 

hexamthylene bis-acetamide inducible 2 

Hexim2

 Hexim2em4Mcwi SS-Hexim2em4Mcwi

Yes

Yes

Yes 

Yes 

Yes 

 Yes

Yes 

Yes 

 

phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 

Prex1 

Prex1em2Mcwi

Yes

Yes

 Yes

Yes 

Yes 

 

 

Yes 

 

5,10-methylenetetrahydrofolate reducatase (NADPH) 

Mthfr 

Mthfrem1Mcwi 

 SS-Mthfrem1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes 

 

Yes 

 

serine/threonine kinase 39, STE20/SPS1 homolog (yeast) 

Stk39 

Stke39em2Mcwi

 SS-Stk39em2Mcwi

Yes

Yes

Yes

Yes

Yes 

Yes 

Yes 

Yes 

 

methionine sulfoxide reductase A 

Msra 

Msraem3Mcwi 

 SS-Msraem3Mcwi

Yes

Yes

Yes

Yes

Yes 

Yes 

Yes 

Yes 

Yes 
Msra Msraem4Mcwi SS-Msraem4Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

pleckstrin homology domain containing, family A member 7 

Plekha7 

Plekha7em1Mcwi 

 SS-Plekha7em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes 

Yes 

Yes 

Yes 
Plekha7 Plekha7em4Mcwi SS-Plekha7em4Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

ATPase, Ca++ transporting, plasma membrane 1 

Atp2b1 

 

Yes

Yes

 Yes

 Yes

Yes 

 

 

 

 

TRAF type zinc finger domain containing 1 

Trafd1 

Trafd1em1Mcwi 

 SS-Trafd1em1Mcwi

Yes

Yes

Yes

Yes 

Yes 

 

 

 

Yes 

 unc-51-like kinase 3 (C. elegans)

Ulk3 

Ulk3em1Mcwi 

 SS-Ulk3em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes 

Yes 

Yes 
Ulk3 Ulk3em4Mcwi SS-Ulk3em4Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

 solute carrier family 30 (zinc transporter), member 8

Slc30a8 

Slc30a8em1Mcwi 

 SS-Slc30a8em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

Yes 

 Yes

Yes 
Slc30a8 Slc30a8em2Mcwi SS-Slc30a8em2Mcwi Yes Yes Yes Yes Yes Yes Yes Yes Yes

 potassium voltage-gated channel, KQT-like subfamily, member 1

Kcnq1 

Kcnq1em14Mcwi 

 SS-Kcnq1em14Mcwi

Yes

Yes

Yes

Yes 

Yes 

Yes 

Yes 

 

Yes 

 cytochrome P450, family 1, subfamily a, polypeptide 1

Cyp1a1 

Cyp1a1em1Mcwi 

 SS-Cyp1a1em1Mcwi

Yes

Yes

Yes

Yes 

Yes 

 Yes

Yes

Yes 

 
Cyp1a1 Cyp1a1em2Mcwi SS-Cyp1a1em2Mcwi Yes Yes Yes Yes Yes Yes Yes Yes
Cyp1a1 Cyp1a1em5Mcwi SS-Cyp1a1em5Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

 cadherin 13

Cdh13 

Cdh13em1Mcwi

 SS-Cdh13em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

Yes 

 

 

 phospholipase C, delta 3

Plcd3 

Plcd3em4Mcwi 

 SS-Plcd3em4Mcwi

Yes

Yes

Yes

Yes

Yes

Yes

Yes 

Yes 

Yes 
Plcd3 Plcd3em7Mcwi SS-Plcd3em7Mcwi Yes Yes Yes Yes Yes Yes Yes Yes Yes

prokineticin receptor 1

Prokr1 

Prokr1em1Mcwi 

 SS-Prokr1em1Mcwi

Yes

Yes

Yes

Yes

Yes

 Yes 

Yes 

 Yes

 Yes
Prokr1 Prokr1em2Mcwi SS-Prokr1em2Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

chloride channel 6 

Clcn6 

Clcn6em2Mcwi 

Yes

Yes

Yes

Yes

 Yes

Yes 

 

Yes

 

 RAS guanyl releasing protein 3 (calcium and DAG-regulated)

Rasgrp3 

Rasgrp3em1Mcwi

 SS-Rasgrp3em1Mcwi

Yes

Yes

Yes

Yes

Yes 

 Yes

Yes 

Yes 

Yes 
Rasgrp3 Rasgrp3em3Mcwi SS-Rasgrp3em3Mcwi Yes Yes Yes Yes Yes Yes

 unc-51-like kinase 4

Ulk4 

Ulk4em3Mcwi 

 SS-Ulk4em3Mcwi

Yes

Yes

Yes

Yes 

Yes 

Yes 

 

 

Yes 

 integrin, alpha 9

Itga9 

Itga9em1Mcwi 

 SS-Itga9emMcwi

Yes

Yes

Yes

Yes 

Yes 

Yes 

 

 

 

 protein tyrosine phosphatase, non-receptor type

Ptpn11 

Ptpn11em1Mcwi 

 SS-Ptpn11em1Mcwi

Yes

Yes

Yes

Yes

Yes

 

 

 

Yes 
Ptpn11 Ptpn11em4Mcwi SS-Ptpn11em1Mcwi Yes Yes Yes Yes Yes Yes

procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 

Plod1 

 Plod1em1Mcwi

 SS-Plod1em1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes 

 Yes

Yes 

 

myostatin 

 Mstn

 Mstnem1Mcwi

 SS-Mstnem1Mcwi

Yes

Yes

Yes

Yes

Yes

Yes 

 Yes

 Yes

Yes 
Mstn Mstnem3Mcwi SS-Mstnem3Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

 transcription factor 7-like 2 (T-cell specific, HMG-box)

 Tcf7l2

 Tcf7l2em1Mcwi

 SS-Tcf7l2em1Mcwi

Yes

Yes

Yes

Yes

Yes 

Yes 

 Yes

Yes 

 

 angiotensin II receptor, type 1a

 Agtr1a

 Agtr1aem1Mcwi

 SS-Agtr1aem1Mcwi  Yes  Yes  Yes  Yes Yes  Yes  Yes Yes  Yes
Agtr1a Agtr1aem5Mcwi SS-Agtr1aem5Mcwi Yes Yes Yes Yes Yes Yes Yes Yes Yes

 cubilin (intrinsic factor-cobalamin receptor)

 Cubn

 

 Yes

Yes 

 Yes  Yes Yes        

 breast carcinoma amplified sequence 3

 Bcas3

  Bcasem4Mcwi SS-Bcasem4Mcwi

 Yes

  Yes Yes  Yes Yes  Yes   Yes  

 N-acetyltransferase 8

 Nat8

  

 Yes

  Yes  Yes  Yes Yes        

 guanylate cyclase 1, soluble, alpha 3

 Gucy1a3

 Gucy1a3em1Mcwi

 SS-Gucy1a3em1Mcwi

 Yes

Yes 

  Yes  Yes  Yes  Yes      

 WD repeat domain 72

 Wdr72

 Wdr72em1Mcwi

 SS-Wdr72em1Mcwi

 Yes

 Yes

 Yes   Yes  Yes  Yes  Yes Yes Yes
Wdr72 Wdr72em2Mcwi SS-Wdr72em2Mcwi Yes Yes Yes Yes Yes Yes Yes Yes

 Alstrom syndrome 1 homolog (human)

 Alms1

Alms1em1Mcwi

 SS-Alms1em1Mcwi

 Yes

 Yes

  Yes  Yes  Yes  Yes      

 prune homolog (Drosophila)

 Prune

 Pruneem1Mcwi

 SS-Pruneem1Mcwi

 Yes

 Yes

 Yes   Yes  Yes       Yes
Prune Pruneem3Mcwi SS-Pruneem3Mcwi Yes Yes Yes Yes Yes Yes

 solute carrier family 6 (neurotransmitter transporter, betaine/GABA), member 12

 Slc6a12

 Slc6a12em1Mcwi

 Yes

Yes 

  Yes  Yes  Yes      Yes  

 stanniocalcin 1

 Stc1

 Stc1em2Mcwi

 Yes

  Yes Yes   Yes  Yes        

 transcription factor Dp-2 (E2F dimerization partner 2)

 Tfdp2

 Tfdp2em2Mcwi

 SS-Tfdp2em2Mcwi

 Yes

  Yes Yes   Yes  Yes Yes    Yes Yes
Tfdp2 Tfdp2em6Mcwi SS-Tfdp2em6Mcwi Yes Yes Yes Yes Yes Yes

 ubiquitin-conjugating enzyme E2Q family member 2

 Ube2q2

 Ube2q2em3Mcwi

 SS-Ube2q2em3Mcwi  Yes Yes   Yes  Yes  Yes     Yes   

fibroblast growth factor 5

Fgf5 

 Fgf5em1Mcwi

 SS-Fgf5em1Mcwi

 Yes

Yes 

Yes 

 Yes 

 Yes

 

 

Yes

 
Fgf5 Fgf5em5Mcwi SS-Fgf5em1Mcwi Yes Yes Yes Yes Yes Yes

cystatin C

 Cst3

Cst3em3Mcwi 

 Yes

Yes 

 Yes

Yes 

Yes 

 

 

Yes 

 

adiponectin, C1Q and collagen domain containing

Adipoq 

 Adipoqem1Mcwi

 Yes

 Yes

 Yes

 Yes

Yes

 

 

Yes 

 
Apipoq Adipoqem2Mcwi Yes Yes Yes Yes Yes Yes

angiotensin II receptor, type 1b

 Agtr1b

 

 Yes

 Yes

 

 

 

 

 

 

 

adrenergic receptor, alpha 2a

Adra2a 

 Adra2aem1Mcwi

 SS-Adra2aem1Mcwi

 Yes

 Yes

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

 

solute carrier family 7 (cationic amino acid transporter, y+ system), member 9

Slc7a9 

 Slc7a9em2Mcwi

 Yes

 Yes

Yes 

Yes

Yes 

 

 

Yes 

 

angiotensin I converting enzyme (peptidyl-dipeptidase A) 1

 Ace

 

 Yes

 Yes

Yes 

Yes 

 

 

 

 

 

solute carrier family 34 (sodium phosphate), member 1

 Slc34a1

 Slc34a1em1Mcwi

 Yes

 Yes

Yes

 

 

 

 

 

 

myeloid-associated differentiation marker-like 2

 Myadml2

 Myadml2em1Mcwi

 Myadml2em1Mcwi

Yes 

 Yes

Yes 

 Yes

 Yes

 

 

 Yes

Yes 
Myadml2 Myadml2em5Mcwi Yes Yes Yes Yes Yes Yes
adducin 2 (beta) Add2  Yes  Yes              
branched chain aminotransferase 1, cytosolic Bcat1  Yes  Yes  Yes Yes          
calcium channel, voltage-dependent, T type, alpha 1H subunit Cacna1h  Yes  Yes  Yes  Yes Yes         
CD247 Cd247 Cd247em1Mcwi  Yes  Yes  Yes  Yes Yes       Yes  

Cd247

 Cd247em3Mcwi Yes Yes Yes Yes Yes Yes
Cd247 Cd247em5Mcwi Yes Yes Yes Yes Yes Yes
catechol-O-methyltransferase Comt Comtem1Mcwi  Yes  Yes Yes   Yes  Yes     Yes   
fibroblast growth factor 1 Fgf1  Yes  Yes  Yes Yes   Yes        
Fyn oncogene related to Src, Fgr, Yes Fyn  Yes  Yes  Yes Yes Yes         
guanine nucleotide binding protein (G protein), beta polypeptide 3 Gnb3 Gnb3em1Mcwi  Yes  Yes  Yes  Yes Yes      Yes   
glutamate receptor, metabotropic 7 Grm7  Yes  Yes  Yes Yes           
potassium inwardly-rectifying channel, subfamily J, member 16 Kcnj16  Yes  Yes  Yes Yes           
lipin 1 Lpin1  Yes  Yes  Yes  Yes Yes        
myosin regulatory light chain interacting protein Mylip Mylipem1Mcwi SS-Mylipem1Mcwi  Yes  Yes  Yes Yes  Yes     Yes  Yes
Mylip Mylipem2Mcwi SS-Mylipem2Mcwi Yes Yes Yes Yes Yes Yes Yes
Mylip Mylipem3Mcwi SS-Mylipem3Mcwi Yes Yes Yes Yes Yes Yes Yes
nitric oxide synthase 3, endothelial cell Nos3  Yes  Yes Yes  Yes           
Phosducin Pdc Pdcem2Mcwi  Yes  Yes Yes Yes  Yes         
Pdc Pdcem4Mcwi Yes Yes Yes Yes Yes
SPARC related molecular calcium binding 2 Smoc2  Yes  Yes              
Sortilin-related VPS10 domain containing receptor 2 Sorcs2 Sorcs2em4Mcwi SS-Sorcs2em4Mcwi  Yes  Yes  Yes Yes Yes     Yes  Yes 
adenosine A2B receptor Adora2b Adora2bem1Mcwi Yes Yes Yes Yes Yes
leptin receptor Lepr Yes Yes Yes Yes
lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase) Lss Yes Yes Yes Yes
ATP-binding cassette, sub-family B (MDR/TAP), member 1B Abcb1b Yes Yes Yes Yes
potassium large conductance calcium-activated, subfamily M, beta member 1 Kcnmb1 Yes

Last updated 2/2/2012

Funding

This project is funded by the National Heart, Lung and Blood Institute of the NIH (5RC2HL101681-02).  

      

 

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