Imperial College London
Alternate

ProfessorGuyRutter

Faculty of Medicine, Department of Medicine

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3340g.rutter Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Anzilotti:2019:10.1038/s41590-018-0295-8,
author = {Anzilotti, C and Swan, DJ and Boisson, B and Deobagkar-Lele, M and Oliveira, C and Chabosseau, P and Engelhardt, KR and Xu, X and Chen, R and Alvarez, L and Berlinguer-Palmini, R and Bull, KR and Cawthorne, E and Cribbs, AP and Crockford, TL and Dang, TS and Fearn, A and Fenech, EJ and de, Jong SJ and Lagerholm, BC and Ma, CS and Sims, D and van, den Berg B and Xu, Y and Cant, AJ and Kleiner, G and Leahy, TR and de, la Morena MT and Puck, JM and Shapiro, RS and van, der Burg M and Chapman, JR and Christianson, JC and Davies, B and McGrath, JA and Przyborski, S and Santibanez, Koref M and Tangye, SG and Werner, A and Rutter, GA and Padilla-Parra, S and Casanova, J-L and Cornall, RJ and Conley, ME and Hambleton, S},
doi = {10.1038/s41590-018-0295-8},
journal = {Nature Immunology},
pages = {350--361},
title = {An essential role for the Zn2+ transporter ZIP7 in B cell development},
url = {http://dx.doi.org/10.1038/s41590-018-0295-8},
volume = {20},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn2+ in modulating B cell receptor signal strength and positive selection.
AU  - Anzilotti,C
AU  - Swan,DJ
AU  - Boisson,B
AU  - Deobagkar-Lele,M
AU  - Oliveira,C
AU  - Chabosseau,P
AU  - Engelhardt,KR
AU  - Xu,X
AU  - Chen,R
AU  - Alvarez,L
AU  - Berlinguer-Palmini,R
AU  - Bull,KR
AU  - Cawthorne,E
AU  - Cribbs,AP
AU  - Crockford,TL
AU  - Dang,TS
AU  - Fearn,A
AU  - Fenech,EJ
AU  - de,Jong SJ
AU  - Lagerholm,BC
AU  - Ma,CS
AU  - Sims,D
AU  - van,den Berg B
AU  - Xu,Y
AU  - Cant,AJ
AU  - Kleiner,G
AU  - Leahy,TR
AU  - de,la Morena MT
AU  - Puck,JM
AU  - Shapiro,RS
AU  - van,der Burg M
AU  - Chapman,JR
AU  - Christianson,JC
AU  - Davies,B
AU  - McGrath,JA
AU  - Przyborski,S
AU  - Santibanez,Koref M
AU  - Tangye,SG
AU  - Werner,A
AU  - Rutter,GA
AU  - Padilla-Parra,S
AU  - Casanova,J-L
AU  - Cornall,RJ
AU  - Conley,ME
AU  - Hambleton,S
DO  - 10.1038/s41590-018-0295-8
EP  - 361
PY  - 2019///
SN  - 1529-2908
SP  - 350
TI  - An essential role for the Zn2+ transporter ZIP7 in B cell development
T2  - Nature Immunology
UR  - http://dx.doi.org/10.1038/s41590-018-0295-8
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30718914
UR  - http://hdl.handle.net/10044/1/66670
VL  - 20
ER  -
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