Tissue expression patterns identify mouse cilia genes

Abstract

In mammals, cilia are critical for development, sensation, cell signaling, sperm motility, and fluid movement. Defects in cilia are causes of several congenital syndromes, providing additional reasons to identify cilia-related genes. We hypothesized that mRNAs selectively abundant in tissues rich in highly ciliated cells encode cilia proteins. Selective abundance in olfactory epithelium, testes, vomeronasal organ, trachea, and lung proved to be an expression pattern uniquely effective in identifying documented cilia-related genes. Known and suspected cilia-related genes were statistically overrepresented among the 99 genes identified, but the majority encoded proteins of unknown function, thereby predicting new cilia-related proteins. Evidence of expression in a highly ciliated cell, the olfactory sensory neuron, exists for 73 of the genes. In situ hybridization for 17 mRNAs confirmed expression of all 17 in olfactory sensory neurons. Most were also detected in vomeronasal sensory neurons and in neighboring tissues rich in ciliated cells such as respiratory epithelium. Immunoreactivity for one of the proteins identified, Spa17, colocalized with acetylated tubulin in the cilia layer of the olfactory epithelium. In contrast, the ciliary rootlet protein, Crocc, was located in discrete structures whose position was consistent with the dendritic knobs of the olfactory sensory neurons. A compilation of >2,000 mouse genes predicted to encode cilia-related proteins revealed a strong correlation (R = 0.99) between the number of studies predicting a gene's involvement in cilia and documented evidence of such involvement, a fact that simplifies the selection of genes for further study of the physiology of cilia.

A large duplication involving the IHH locus mimics acrocallosal syndrome

“…CCDC108 is a putative ciliary protein, and although a ciliary function has not been ascertained for CCDC108, it has been ascribed to many other members of the CCDC gene family, like CCDC39, CCDC40 and others. 13 As yet no human phenotype has been depicted for alterations in CCDC108. Seen as the 5¢ breakpoint of these tandem duplications lies within CCDC108, it appears an unlikely candidate to contribute to the phenotype in our cases, because gene dosage of this gene would be expected to be normal.…”

Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella

“…40,41 CFAP65 contains a MSP (major sperm protein) domain that is present in sperm-specific proteins, and its mouse ortholog has been reported to be a putative ciliary protein. 44 Furthermore, CFAP65 is expressed specifically in sexually mature male mice but is absent in juvenile mice. 45 Although a knockout mouse model was not generated for CFAP65 in this study, evidence from previous studies strongly supports the roles of CFAP65 in spermatogenesis and flagellar development.…”

Subventricular Zone-Mediated Ependyma Repair in the Adult Mammalian Brain

“…and Fuchs, 2006), cilia (acetylated tubulin) (McClintock et al, 2008), and intermediate filaments of astrocytes (glial fibrillary acidic protein, GFAP). In young mice, ␤-catenin staining revealed the cellular outline of the ependymal cells, whereas acetylated tubulin decorated tufts of cilia associated with each ependymal cell (Fig.…”