RGD Reference Report - Role of Alström syndrome 1 in the regulation of blood pressure and renal function. - Rat Genome Database

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Role of Alström syndrome 1 in the regulation of blood pressure and renal function.

Authors: Jaykumar, Ankita Bachhawat  Caceres, Paulo S  King-Medina, Keyona N  Liao, Tang-Dong  Datta, Indrani  Maskey, Dipak  Naggert, Jürgen K  Mendez, Mariela  Beierwaltes, William H  Ortiz, Pablo A 
Citation: Jaykumar AB, etal., JCI Insight. 2018 Nov 2;3(21). pii: 95076. doi: 10.1172/jci.insight.95076.
RGD ID: 151361229
Pubmed: PMID:30385718   (View Abstract at PubMed)
PMCID: PMC6238740   (View Article at PubMed Central)
DOI: DOI:10.1172/jci.insight.95076   (Journal Full-text)

Elevated blood pressure (BP) and renal dysfunction are complex traits representing major global health problems. Single nucleotide polymorphisms identified by genome-wide association studies have identified the Alström syndrome 1 (ALMS1) gene locus to render susceptibility for renal dysfunction, hypertension, and chronic kidney disease (CKD). Mutations in the ALMS1 gene in humans causes Alström syndrome, characterized by progressive metabolic alterations including hypertension and CKD. Despite compelling genetic evidence, the underlying biological mechanism by which mutations in the ALMS1 gene lead to the above-mentioned pathophysiology is not understood. We modeled this effect in a KO rat model and showed that ALMS1 genetic deletion leads to hypertension. We demonstrate that the link between ALMS1 and hypertension involves the activation of the renal Na+/K+/2Cl- cotransporter NKCC2, mediated by regulation of its endocytosis. Our findings establish a link between the genetic susceptibility to hypertension, CKD, and the expression of ALMS1 through its role in a salt-reabsorbing tubular segment of the kidney. These data point to ALMS1 as a potentially novel gene involved in BP and renal function regulation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of endocytosis  IMP 151361229 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IDA 151361229protein C-terminus bindingRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Alms1  (ALMS1, centrosome and basal body associated protein)
Alms1em1Mcwi  (Alstrom syndrome 1 homolog (human); zinc finger nuclease induced mutant 1, Medical College of Wisconsin)

SS-Alms1em1Mcwi-/-  (SS-Alms1em1Mcwi-/Alms1em1Mcwi-)

Objects referenced in this article
Strain SS-Alms1em1Mcwi null Rattus norvegicus

Additional Information