Document Type
Article
Publication Date
9-1-2023
Original Citation
Yang C,
Harafuji N,
Caldovic L,
Yu W,
Boddu R,
Bhattacharya S,
Barseghyan H,
Gordish-Dressman H,
Foreman O,
Bebok Z,
Eicher E,
Guay-Woodford L.
Pkhd1 J Mol Med (Berl). 2023;101(9):1141-51.
Keywords
JMG, Child, Preschool, Mice, Humans, Animals, Polycystic Kidney, Autosomal Recessive, Kidney, Mutation, Liver Diseases, Transcription Factors, RNA, Messenger, Receptors, Cell Surface
JAX Source
J Mol Med (Berl). 2023;101(9):1141-51.
ISSN
1432-1440
PMID
37584738
DOI
https://doi.org/10.1007/s00109-023-02351-2
Grant
This work was supported by NIH grants RR01183 and GM20919 to EME; NIH grant DK121530 and a gift from the Moran Family Foundation to LGW.
Abstract
Autosomal-recessive polycystic kidney disease (ARPKD; MIM #263200) is a severe, hereditary, hepato-renal fibrocystic disorder that causes early childhood morbidity and mortality. Mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene, which encodes the protein fibrocystin/polyductin complex (FPC), cause all typical forms of ARPKD. Several mouse lines carrying diverse, genetically engineered disruptions in the orthologous Pkhd1 gene have been generated, but none expresses the classic ARPKD renal phenotype. In the current study, we characterized a spontaneous mouse Pkhd1 mutation that is transmitted as a recessive trait and causes cysticliver (cyli), similar to the hepato-biliary disease in ARPKD, but which is exacerbated by age, sex, and parity. We mapped the mutation to Chromosome 1 and determined that an insertion/deletion mutation causes a frameshift within Pkhd1 exon 48, which is predicted to result in a premature termination codon (UGA). Pkhd1
Comments
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