DFNB31

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Deafness, autosomal recessive 31
Protein DFNB31 PDB 1uez.png
PDB rendering based on 1uez.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DFNB31 ; CIP98; USH2D; WHRN; WI
External IDs OMIM607928 MGI2682003 HomoloGene18739 GeneCards: DFNB31 Gene
RNA expression pattern
PBB GE DFNB31 221887 s at tn.png
PBB GE DFNB31 47553 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 25861 73750
Ensembl ENSG00000095397 ENSMUSG00000039137
UniProt Q9P202 Q80VW5
RefSeq (mRNA) NM_001083885 NM_001008791
RefSeq (protein) NP_001077354 NP_001008791
Location (UCSC) Chr 9:
117.16 – 117.27 Mb
Chr 4:
63.41 – 63.5 Mb
PubMed search [1] [2]

Whirlin is a protein that in humans is encoded by the DFNB31 gene.[1][2][3]

In rat brain, WHRN interacts with a calmodulin-dependent serine kinase, CASK, and may be involved in the formation of scaffolding protein complexes that facilitate synaptic transmission in the central nervous system (CNS).[4] Mutations in this gene, also known as WHRN, cause autosomal recessive deafness.[3]

Model organisms[edit]

Model organisms have been used in the study of WHRN function. A conditional knockout mouse line, called Whrntm1a(EUCOMM)Wtsi[8][9] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][13] Twenty tests were carried out on mutant mice and two significant abnormalities were observed.[6] Whrntm1a(EUCOMM)Wtsi homozygote mice show a moderate to severe hearing loss at 14 weeks. Female homozygous mutant animals also displayed an increased thermal nociceptive threshold in a hot plate test.[6]

References[edit]

  1. ^ Mburu P, Mustapha M, Varela A, Weil D, El-Amraoui A, Holme RH, Rump A, Hardisty RE, Blanchard S, Coimbra RS, Perfettini I, Parkinson N, Mallon AM, Glenister P, Rogers MJ, Paige AJ, Moir L, Clay J, Rosenthal A, Liu XZ, Blanco G, Steel KP, Petit C, Brown SD (Aug 2003). "Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31". Nat Genet 34 (4): 421–8. doi:10.1038/ng1208. PMID 12833159. 
  2. ^ Ebermann I, Scholl HP, Charbel Issa P, Becirovic E, Lamprecht J, Jurklies B, Millan JM, Aller E, Mitter D, Bolz H (Mar 2007). "A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss". Hum Genet 121 (2): 203–11. doi:10.1007/s00439-006-0304-0. PMID 17171570. 
  3. ^ a b "Entrez Gene: DFNB31 deafness, autosomal recessive 31". 
  4. ^ Yap CC, Liang F, Yamazaki Y et al. (2003). "CIP98, a novel PDZ domain protein, is expressed in the central nervous system and interacts with calmodulin-dependent serine kinase". J. Neurochem. 85 (1): 123–34. doi:10.1046/j.1471-4159.2003.01647.x. PMID 12641734. 
  5. ^ "Hot plate data for Whrn". Wellcome Trust Sanger Institute. 
  6. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  7. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  8. ^ "International Knockout Mouse Consortium". 
  9. ^ "Mouse Genome Informatics". 
  10. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  11. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  12. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  13. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Further reading[edit]

External links[edit]