an n-ethyl-n-nitrosourea (enu)-induced dominant negative mutation in the jak3 kinase protects against cerebral malaria全身的n-ethyl-n-nitrosourea(enu表示)主导负突变jak3激酶对脑型疟疾的保护.pdfVIP
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an n-ethyl-n-nitrosourea (enu)-induced dominant negative mutation in the jak3 kinase protects against cerebral malaria全身的n-ethyl-n-nitrosourea(enu表示)主导负突变jak3激酶对脑型疟疾的保护
An N-Ethyl-N-Nitrosourea (ENU)-Induced Dominant
Negative Mutation in the JAK3 Kinase Protects against
Cerebral Malaria
Silayuv E. Bongfen1,4, Ian-Gael Rodrigue-Gervais2,4, Joanne Berghout1,4, Sabrina Torre3,4, Pablo
5 3,4 3,4 3 3
Cingolani , Sean A. Wiltshire , Gabriel A. Leiva-Torres , Louis Letourneau , Robert Sladek , Mathieu
5 6 7,8 4,7 3,4 2,4
Blanchette , Mark Lathrop , Marcel A. Behr , Samantha Gruenheid , Silvia M. Vidal , Maya Saleh ,
Philippe Gros1,3,4*
1 Department of Biochemistry, McGill University, Montreal, Canada, 2 Department of Medicine, McGill University, Montreal, Canada, 3 Department of Human Genetics,
McGill University, Montreal, Canada, 4 Complex Traits Group, McGill University, Montreal, Canada, 5 School of Computer Science, McGill University, Montreal, Canada,
´ ´
6 Institut de Genomique, Centre National de Genotypage, Evry, France, 7 Department of Microbiology and Immunology, McGill University, Montreal, Canada, 8 The McGill
University Health Center, Montreal, Canada
Abstract
Cerebral malaria (CM) is a lethal neurological complication of malaria. We implemented a genome-wide screen in
mutagenized mice to identify host proteins involved in CM pathogenesis and whose inhibition may be of therapeutic value.
One pedigree (P48) segregated a resistance trait whose CM-protective effect was fully penetrant, mapped to chromosome
8, and identified by genome sequencing as homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus-
asso
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