RGD Reference Report - The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. - Rat Genome Database

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The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease.

Authors: Liu, Z  Lee, J  Krummey, S  Lu, W  Cai, H  Lenardo, MJ 
Citation: Liu Z, etal., Nat Immunol. 2011 Oct 9. doi: 10.1038/ni.2113.
RGD ID: 5508401
Pubmed: PMID:21983832   (View Abstract at PubMed)
PMCID: PMC4140245   (View Article at PubMed Central)
DOI: DOI:10.1038/ni.2113   (Journal Full-text)

Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colitis  ISOLrrk2 (Mus musculus)5508401; 5508401 RGD 
colitis  IMP 5508401 RGD 
Crohn's disease  IAGP 5508401DNA:point mutation: :p.T2397M (rs3761863) (human)RGD 
Crohn's disease  ISOLRRK2 (Homo sapiens)5508401; 5508401DNA:point mutation: :p.T2397M (rs3761863) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lrrk2  (leucine-rich repeat kinase 2)

Genes (Mus musculus)
Lrrk2  (leucine-rich repeat kinase 2)

Genes (Homo sapiens)
LRRK2  (leucine rich repeat kinase 2)


Additional Information