ArticleHuman molecular genetics2013
Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 107 citations in OpenAlex.
- CEP290 deficiency disrupts ciliary axonemal architecture in human iPSC-derived brain organoids.Journal of cell science · 2025Article
- Cleavage of the Meckel-Gruber syndrome protein TMEM67 by ADAMTS9 uncouples Wnt signaling and ciliogenesis.Nature communications · 2025Article
- A differential requirement for ciliary transition zone proteins in human and mouse neural progenitor fate specification.Nature communications · 2025Article
- SMPD4-mediated sphingolipid metabolism regulates brain and primary cilia development.Development (Cambridge, England) · 2024Article
- A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease.Nature communications · 2024Article
- A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts.BMC medical genomics · 2024Article
- A case of Joubert syndrome caused by novel compound heterozygous variants in theThe Journal of international medical research · 2023Article
- Kinase Inhibitors in Genetic Diseases.International journal of molecular sciences · 2023Review
- The Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies.Annual review of genomics and human genetics · 2022Review
- Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components.Journal of cell science · 2022Article
- Primary cilia and ciliary signaling pathways in aging and age-related brain disorders.Neurobiology of disease · 2022Review
- Genetic and phenotypic heterogeneity in KIAA0753-related ciliopathies.American journal of medical genetics. Part A · 2022Article
- Primary Cilia in Pancreatic β- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme.Frontiers in endocrinology · 2022Review
- Structure of the human Meckel-Gruber protein Meckelin.Science advances · 2021Article
- Prenatal alcohol exposure disrupts Sonic hedgehog pathway and primary cilia genes in the mouse neural tube.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Clinical and genetic heterogeneity of primary ciliopathies (Review).International journal of molecular medicine · 2021Review
- Smoothened and ARL13B are critical in mouse for superior cerebellar peduncle targeting.Genetics · 2021Article
- Genetic and epigenetic mechanisms in the development of congenital heart diseases.World journal of pediatric surgery · 2021Review
- TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human.Frontiers in molecular neuroscience · 2021Article
- Genotype Phenotype Correlation and Variability in Microcephaly Associated With Chorioretinopathy or Familial Exudative Vitreoretinopathy.Investigative ophthalmology & visual science · 2020Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
The ciliopathies are a group of heterogeneous diseases with considerable variations in phenotype for allelic conditions such as Meckel-Gruber syndrome (MKS) and Joubert syndrome (JBTS) even at the inter-individual level within families. In humans, mutations in TMEM67 (also known as MKS3) cause both MKS and JBTS, with TMEM67 encoding the orphan receptor meckelin (TMEM67) that localizes to the ciliary transition zone. We now describe the Tmem67(tm1(Dgen/H)) knockout mouse model that recapitulates the brain phenotypic variability of these human ciliopathies, with categorization of Tmem67 mutant animals into two phenotypic groups. An MKS-like incipient congenic group (F6 to F10) manifested very variable neurological features (including exencephaly, and frontal/occipital encephalocele) that were associated with the loss of primary cilia, diminished Shh signalling and dorsalization of the caudal neural tube. The 'MKS-like' group also had high de-regulated canonical Wnt/β-catenin signalling associated with hyper-activated Dishevelled-1 (Dvl-1) localized to the basal body. Conversely, a second fully congenic group (F > 10) had less variable features pathognomonic for JBTS (including cerebellar hypoplasia), and retention of abnormal bulbous cilia associated with mild neural tube ventralization. The 'JBTS-like' group had de-regulated low levels of canonical Wnt signalling associated with the loss of Dvl-1 localization to the basal body. Our results suggest that modifier alleles partially determine the variation between MKS and JBTS, implicating the interaction between Dvl-1 and meckelin, or other components of the ciliary transition zone. The Tmem67(tm1(Dgen/H)) line is unique in modelling the variable expressivity of phenotypes in these two ciliopathies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.