| 2011 |
Pkd1l1 physically interacts with Pkd2 (co-immunoprecipitation), co-localises with Pkd2 in the cilium of mouse node cells, and both proteins act downstream of nodal flow to establish left-right asymmetry; loss of Pkd1l1 phenocopies loss of Pkd2, with failure to activate asymmetric gene expression at the node and in the lateral plate mesoderm, and right isomerism of the lungs, despite normal node/cilia morphology and motility. |
Biochemical co-immunoprecipitation, cell biological co-localisation in cilia, phenotypic comparison of Pkd1l1 and Pkd2 point mutants (mouse genetics) |
Development (Cambridge, England) |
High |
21307093
|
| 2011 |
In medaka (zebrafish-related model), pkd1l1 is expressed exclusively in Kupffer's vesicle (KV); Pkd1l1 and Pkd2 interact and interdependently co-localise at motile KV cilia; all KV cilia contain Pkd1l1, Pkd2, and left-right dynein and are motile, indicating Pkd1l1-Pkd2 complexes function as the nodal flow sensor within motile cilia rather than in a separate immotile sensory population. |
Genetic mapping of medaka left-right mutant abecobe (abc) to pkd1l1; immunofluorescence co-localisation; interaction assay; ciliary motility analysis |
Development (Cambridge, England) |
High |
21307098
|
| 2010 |
Pkd1l1-knockout mice develop situs inversus without hydrocephalus, sinusitis, or male infertility, indicating that Pkd1l1 loss causes laterality defects through dysfunction of mechanosensory (immotile) cilia rather than motile cilia, consistent with a sensory role analogous to Pkd1 in renal primary cilia. |
Constitutive Pkd1l1 knockout mouse; phenotype battery screening; comparative pathology with Dpcd/Poll and Nme7 knockouts that have motile-cilia defects |
Veterinary pathology |
Medium |
20080492
|
| 2002 |
PKD1L1 encodes a 2849-amino-acid polycystin-1-like protein with two Ig-like PKD domains, a REJ domain, a GPS motif, a LH2/PLAT domain, a coiled-coil domain, and 11 putative transmembrane domains; it is expressed in human testis, fetal and adult heart, and in mouse Leydig cells of the testis. |
Full-length cDNA sequencing from human testis; dot-blot and RT-PCR expression analysis; in situ hybridization; FISH chromosomal mapping |
Genomics |
Medium |
11863367
|
| 2016 |
Bi-allelic loss-of-function mutations in human PKD1L1 cause laterality defects (situs inversus totalis and heterotaxy with complex congenital heart malformations); a missense mutation p.Cys1691Ser disrupts a conserved cysteine in the GPS motif predicted to be required for a disulfide bridge essential for proper GPS-motif folding, establishing the GPS motif as functionally critical. |
Whole-exome sequencing of two unrelated families; molecular modelling of GPS motif disulfide bridge; splice-site mutation prediction |
American journal of human genetics |
Medium |
27616478
|
| 2024 |
Pkd1l1 deficiency in biliary epithelial cells reduces primary cilia on cholangiocytes, decreases expression of ciliary Hedgehog-pathway signalling genes (Gli1, Gli2, Ptch1, Ptch2), and increases fibrosis/ECM-remodelling genes (Tgfα, Cdkn1a, Hb-egf, Fgfr3, Pdgfc, Mmp12, Mmp15), leading to bile duct hypertrophy, fibrosis, and delayed biliary drainage; pharmacological inhibition of GLI1 with Gant61 recapitulates the Pkd1l1-deficient biliary phenotype, placing Pkd1l1 upstream of ciliary Hedgehog/GLI1 signalling in bile duct homeostasis. |
Constitutive and conditional Pkd1l1 knockout mice; cholangiography; DDC dietary challenge; immunofluorescence for primary cilia; gene expression analysis; GLI1 inhibitor (Gant61) pharmacological epistasis |
Journal of hepatology |
Medium |
38460793
|
| 2023 |
Liver-specific (hepatoblast) deletion of Pkd1l1 causes reduced primary cilia on cholangiocytes, delayed biliary maturation, progressive cholangiocyte proliferation, peribiliary fibroinflammation, and arterial hypertrophy, demonstrating a cell-autonomous role for Pkd1l1 in intrahepatic biliary ciliogenesis and duct morphogenesis. |
CRISPR-based conditional loxP Pkd1l1 allele crossed with AFP-Cre for liver-specific knockout; immunofluorescence; electron microscopy; RNA sequencing; bile duct ligation challenge |
Hepatology (Baltimore, Md.) |
Medium |
36645229
|
| 2023 |
Loss of pkd1l1 in zebrafish causes left-right patterning defects and reduces biliary epithelial cell number and intrahepatic biliary network density, demonstrating a conserved role for Pkd1l1 in biliary tree development beyond laterality. |
CRISPR/Cas9-generated pkd1l1hsc117 zebrafish allele; fluorescent biliary functional assay (PED6 accumulation); immunofluorescence quantification of biliary epithelial cells |
Disease models & mechanisms |
Medium |
37675454
|
| 2024 |
PKD1L1 missense variants implicated in congenital chylothorax cause protein dysfunction without mislocalization, whereas a loss-of-function frameshift variant causes protein mislocalization; Pkd1l1 mutant mouse embryos display pleural effusion and altered lymphatic vessel morphology at E14.5, identifying a role for PKD1L1 in lymphatic vessel development. |
Exome sequencing; immunofluorescence assessment of PKD1L1 protein localization for identified variants; immunofluorescence staining of lymphatic vessels in Pkd1l1 mutant mouse embryos at E14.5 |
Cells |
Low |
38247840
|