RGD Reference Report - Meckelin 3 is necessary for photoreceptor outer segment development in rat Meckel syndrome. - Rat Genome Database

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Meckelin 3 is necessary for photoreceptor outer segment development in rat Meckel syndrome.

Authors: Tiwari, S  Hudson, S  Gattone VH, 2ND  Miller, C  Chernoff, EA  Belecky-Adams, TL 
Citation: Tiwari S, etal., PLoS One. 2013;8(3):e59306. doi: 10.1371/journal.pone.0059306. Epub 2013 Mar 13.
RGD ID: 11535084
Pubmed: PMID:23516626   (View Abstract at PubMed)
PMCID: PMC3596335   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0059306   (Journal Full-text)

Ciliopathies lead to multiorgan pathologies that include renal cysts, deafness, obesity and retinal degeneration. Retinal photoreceptors have connecting cilia joining the inner and outer segment that are responsible for transport of molecules to develop and maintain the outer segment process. The present study evaluated meckelin (MKS3) expression during outer segment genesis and determined the consequences of mutant meckelin on photoreceptor development and survival in Wistar polycystic kidney disease Wpk/Wpk rat using immunohistochemistry, analysis of cell death and electron microscopy. MKS3 was ubiquitously expressed throughout the retina at postnatal day 10 (P10) and P21. However, in the mature retina, MKS3 expression was restricted to photoreceptors and the retinal ganglion cell layer. At P10, both the wild type and homozygous Wpk mutant retina had all retinal cell types. In contrast, by P21, cells expressing rod- and cone-specific markers were fewer in number and expression of opsins appeared to be abnormally localized to the cell body. Cell death analyses were consistent with the disappearance of photoreceptor-specific markers and showed that the cells were undergoing caspase-dependent cell death. By electron microscopy, P10 photoreceptors showed rudimentary outer segments with an axoneme, but did not develop outer segment discs that were clearly present in the wild type counterpart. At p21 the mutant outer segments appeared much the same as the P10 mutant outer segments with only a short axoneme, while the wild-type controls had developed outer segments with many well-organized discs. We conclude that MKS3 is not important for formation of connecting cilium and rudimentary outer segments, but is critical for the maturation of outer segment processes.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
photoreceptor cell outer segment organization  IMP 11535084 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axoneme located_inIDA 11535084 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
photoreceptor outer segment degeneration  IAGP 11535084 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tmem67  (transmembrane protein 67)

Additional Information