Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We used a genome-wide screen in
N
-ethyl-
N
-nitrosourea (ENU)-mutagenized mice to identify genes in which recessive loss-of-function mutations protect against pathological neuroinflammation. We identified an R367Q mutation in the
ZBTB7B
(ThPOK) protein in which homozygosity causes protection against experimental cerebral
malaria
(ECM) caused by infection with
Plasmodium berghei
ANKA.
Zbtb7b
R367Q
homozygous mice show a defect in the lymphoid compartment expressed as severe reduction in the number of single-positive CD4 T cells in the thymus and in the periphery, reduced brain infiltration of proinflammatory leukocytes in
P. berghei
ANKA-infected mice, and reduced production of proinflammatory cytokines by primary T cells
ex vivo
and
in vivo
Dampening of proinflammatory immune responses in
Zbtb7b
R367Q
mice is concomitant to increased susceptibility to infection with avirulent (
Mycobacterium bovis
BCG) and virulent (
Mycobacterium tuberculosis
H37Rv) mycobacteria. The R367Q mutation maps to the first DNA-binding zinc finger domain of ThPOK and causes loss of base contact by R367 in the major groove of the DNA, which is predicted to impair DNA binding. Global immunoprecipitation of ThPOK-containing chromatin complexes coupled to DNA sequencing (ChIP-seq) identified transcriptional networks and candidate genes likely to play key roles in CD4
+
CD8
+
T cell development and in the expression of lineage-specific functions of these cells. This study highlights ThPOK as a global regulator of immune function in which alterations may affect normal responses to infectious and inflammatory stimuli.
...
PMID:ZBTB7B (ThPOK) Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis. 3179 77
