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Abstract: FR-PO283

Conserved Glycine Rich (G8) Domains in Zebrafish Fibrocystin-L (FPC-L) Paralogs Identify a Tractable Experimental System for Functional Studies of PKHD1-Encoded FPC

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Gulati, Ashima, Children’s National Research Institute, Washington, District of Columbia, United States
  • Swift, Matthew R., Georgetown University, Washington, District of Columbia, United States
  • Glasgow, Eric, Georgetown University, Washington, District of Columbia, United States
  • Guay-Woodford, Lisa M., Children’s National Research Institute, Washington, District of Columbia, United States

Functional evaluation of FPC, the major protein underlying ARPKD is limited because rodent models do not recapitulate the human renal phenotype. Homology analyses and phylogenic expression identify FPC-L encoded by PKHD1L1 as the likely ancestral protein to PKHD1-encoded FPC. We compared the homology of FPC predicted domains with its ancestral protein, FPC-L. While zebrafish lack FPC, the phylogenetic conservation of specific N-terminal domains in FPC-L, suggests that zebrafish could serve as a tractable system to investigate domain-specific motifs relevant to FPC function.


Informatics analysis: FPC-L, FPC identity/similarity scores across evolutionary timescale. Zebrafish embryo FPC-L expression: whole mount in situ hybridization for pkhd1l1.1 and pkhd1l1.2.


FPC-L and FPC share two conserved glycine-rich G8 domains that are relatively unique to these protein families. The first G8 domain spanning 122 amino acids exhibits two times the identity (50% identical, 63% similar) when compared to overall human FPC-L and FPC homology (25% identity, 44% similarity). FPC-L zebrafish paralogs are widely expressed at various stages during embryonic development in a reproducible pattern (Figure). FPC-L expression mirrors that of pkd2 and other ciliary proteins that are widely expressed at a low level in most zebrafish tissues.


The conservation of two unique G8 domains in FPC and its ancestral protein, FPC-L, over the evolutionary span of vertebrate aquatic to terrestrial transition supports the biologic relevance of these domains. Zebrafish present a tractable experimental model to interrogate the function of these highly conserved domains, and provide new insights into the functional biology of FPC-L and FPC N-termini.

Tailbud to 24 hpf zebrafish embryos, pkhd1l1.2 is ubiquitous with prominent cranial staining


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