RGD Reference Report - Leucine-rich repeat kinase 2 (LRRK2)-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis. - Rat Genome Database

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Leucine-rich repeat kinase 2 (LRRK2)-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis.

Authors: Ness, Daniel  Ren, Zhao  Gardai, Shyra  Sharpnack, Douglas  Johnson, Victor J  Brennan, Richard J  Brigham, Elizabeth F  Olaharski, Andrew J 
Citation: Ness D, etal., PLoS One. 2013 Jun 14;8(6):e66164. doi: 10.1371/journal.pone.0066164. Print 2013.
RGD ID: 13462048
Pubmed: PMID:23799078   (View Abstract at PubMed)
PMCID: PMC3682960   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0066164   (Journal Full-text)

Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV) and Streptococcus pneumoniae. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal circulating aspartate transaminase level  IMP 13462048; 13462048; 13462048 RGD 
decreased circulating alanine transaminase level  IMP 13462048; 13462048; 13462048 RGD 
decreased circulating aspartate transaminase level  IMP 13462048 RGD 
decreased circulating bilirubin level  IMP 13462048; 13462048; 13462048 RGD 
decreased circulating chloride level  IMP 13462048; 13462048; 13462048 RGD 
decreased circulating potassium level  IMP 13462048; 13462048; 13462048 RGD 
decreased circulating prolactin level  IMP 13462048; 13462048; 13462048 RGD 
decreased circulating triglyceride level  IMP 13462048; 13462048; 13462048 RGD 
decreased eosinophil cell number  IMP 13462048; 13462048; 13462048 RGD 
decreased erythrocyte cell number  IMP 13462048 RGD 
decreased hematocrit  IMP 13462048 RGD 
decreased hemoglobin content  IMP 13462048; 13462048; 13462048 RGD 
decreased lymphocyte cell number  IMP 13462048; 13462048; 13462048 RGD 
hypersecretion of adrenocorticotropin  IMP 13462048; 13462048; 13462048 RGD 
increased circulating cholesterol level  IMP 13462048 RGD 
increased circulating luteinizing hormone level  IMP 13462048; 13462048; 13462048 RGD 
increased circulating serum albumin level  IMP 13462048; 13462048; 13462048 RGD 
increased circulating testosterone level  IMP 13462048 RGD 
increased insulin secretion  IMP 13462048 RGD 
increased susceptibility to weight gain  IMP 13462048; 13462048; 13462048 RGD 

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Rat Strains:
Clinical Measurements:
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Measurement Methods:
Objects Annotated

Genes (Rattus norvegicus)
Lrrk2  (leucine-rich repeat kinase 2)
Lrrk2em1Sage  (leucine-rich repeat kinase 2; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Strains
LE-Lrrk2em1Sage-/-  (NA)


Additional Information