RGD Reference Report - Actin -related protein 3 (Arp3) is mutated in proteinuric BUF/Mna rats. - Rat Genome Database

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Actin -related protein 3 (Arp3) is mutated in proteinuric BUF/Mna rats.

Authors: Akiyama, K  Morita, H  Suetsugu, S  Kuraba, S  Numata, Y  Yamamoto, Y  Inui, K  Ideura, T  Wakisaka, N  Nakano, K  Oniki, H  Takenawa, T  Matsuyama, M  Yoshimura, A 
Citation: Akiyama K, et al., Mamm Genome. 2008 Jan;19(1):41-50. Epub 2007 Dec 7.
RGD ID: 2292230
Pubmed: PMID:18064521   (View Abstract at PubMed)
DOI: DOI:10.1007/s00335-007-9078-5   (Journal Full-text)

The BUF/Mna strain of rat is a model of focal and segmental glomerulosclerosis (FSGS) in which a quantitative trait locus (QTL) for proteinuria, Pur1, has been identified. The aim of the present study was to identify candidates for the Pur1 gene. To narrow the Pur1 QTL, we performed fine QTL mapping and single nucleotide polymorphism (SNP) genotyping. To identify candidate genes, sequencing and gene-expression analyses of all genes contained in the narrowed locus were conducted. The narrowed Pur1 region contained 25 genes. Among these genes, only the Arp3 gene was mutated in the BUF/Mna strain; it contained a missense mutation that caused an (L)111(F) substitution. This leucine is conserved across species. Gene-expression analysis failed to identify any other candidate genes for Pur1. Arp3-mediated actin assembly abnormalities were visible in immunohistochemical and electron microscopic examinations of podocytes in old BUF/Mna rats. Taken together, these data suggest that Arp3 is a candidate for the Pur1 gene. This observation is consistent with our growing recognition that abnormal signaling-induced assembly of actin in podocytes leads to the development of FSGS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
focal segmental glomerulosclerosis  ISOActr3 (Rattus norvegicus)2292230; 2292230DNA:missense mutation:cds:p.L111F (rat)RGD 
focal segmental glomerulosclerosis  IAGP 2292230DNA:missense mutation:cds:p.L111F (rat)RGD 
proteinuria  IAGP 2292230 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIWASL (Homo sapiens)2292230 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased urine protein level  IAGP 2292230DNA:missense mutation:cds:p.L111FRGD 
increased urine protein level  IDA 2292230 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Actr3  (actin related protein 3)

Genes (Mus musculus)
Actr3  (ARP3 actin-related protein 3)

Genes (Homo sapiens)
ACTR3  (actin related protein 3)

QTLs
Pur16  (Proteinuria QTL 16)

Strains
BUF/Mna  (NA)
WKY/NCrlCrlj  (NA)

Objects referenced in this article
QTL Pur1 Proteinuria QTL 1 Rattus norvegicus

Additional Information