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The circling behavior of the deafblind LEW-ci2 rat is linked to a segment of RNO10 containing Myo15 and Kcnj12

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Abstract

The LEW/Ztm-ci2 rat is an autosomal recessive mutant that displays circling behavior, deafness, progressive retinopathy, locomotor hyperactivity, ataxia, and opisthotonus. We performed a genome-wide scan of a (LEW/Ztm-ci2 × BN/Ztm) F1 × LEW/Ztm-ci2 backcross population with anonymous microsatellite markers to analyze the genetics of this mutant rat. This linkage analysis demonstrated a very strong association of RNO10 SSLP markers to the phenotype with a core region in the central part of the chromosome. The knowledge of genes mapping to this part of the rat genome and their linkage to SSLP markers is still poor. We developed SSLP markers closely linked to genes, which might be responsible for the mutant phenotype by using the growing amount of rat-specific DNA sequences available at World Wide Web databases. Application of this method facilitated the search for candidate genes for the phenotype of the LEW-ci2 rat. We were able to map Myo15 and its neighboring genes, Znf179 and Aldh3a1, to the region of interest and Myo1c to a more distal location on RNO10. Further rat BAC clones were used to create a physical map of the region of interest. This map revealed the position of further genes. Among those is Kcnj12. Owing to their localization on RNO10 and their involvement in a similar pathology in human and mouse, Myo15 and Kcnj12 can be regarded as candidate genes for the deafblind phenotype of the LEW-ci2 rat.

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References

  1. SF Altschul W Gish W Miller EW Myers DJ Lipman (1990) ArticleTitleBasic local alignment search tool. J Mol Biol 215 403–410 Occurrence Handle10.1006/jmbi.1990.9999 Occurrence Handle1:CAS:528:DyaK3MXitVGmsA%3D%3D Occurrence Handle2231712

    Article  CAS  PubMed  Google Scholar 

  2. DW Anderson FJ Probst IA Belyantseva RA Fridell L Beyer et al. (2000) ArticleTitleThe motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Hum Mol Genet 9 1729–1738

    Google Scholar 

  3. Y Andoh T Kuramoto N Yokoi T Maihara K Kitada et al. (1998) ArticleTitleCorrelation between genetic and cytogenetic maps of the rat. Mamm Genome 9 287–293 Occurrence Handle10.1007/s003359900750 Occurrence Handle1:CAS:528:DyaK1cXit1aisrw%3D Occurrence Handle9530624

    Article  CAS  PubMed  Google Scholar 

  4. DC Asman K Takimoto HC Pitot R Lindahl (1993) ArticleTitlePreliminary characterization of the rat class 3 aldehyde dehydrogenase gene. Adv Exp Med Biol 328 81–86 Occurrence Handle1:CAS:528:DyaK3sXlsFejurs%3D Occurrence Handle8493943

    CAS  PubMed  Google Scholar 

  5. M Bahler R Kroschewski HE Stoffler T Behrmann (1994) ArticleTitleRat myr 4 defines a novel subclass of myosin I: identification, distribution, localization, and mapping of calmodulin-binding sites with differential calcium sensitivity. J Cell Biol 126 375–389 Occurrence Handle1:STN:280:ByuA3cfis1w%3D Occurrence Handle8034741

    CAS  PubMed  Google Scholar 

  6. M Fedrowitz H Potschka A Richter W Löscher (2000) ArticleTitleA microdialysis study of striatal dopamine release in the circling rat, a genetic animal model with spontaneous lateralized rotational behavior. Neuroscience 97 69–77 Occurrence Handle10.1016/S0306-4522(00)00040-3 Occurrence Handle1:CAS:528:DC%2BD3cXisFGhtbk%3D Occurrence Handle10771340

    Article  CAS  PubMed  Google Scholar 

  7. S Inoue A Orimo T Saito K Ikeda K Sakata et al. (1997) ArticleTitleA novel RING finger protein, BFP, predominantly expressed in the brain. Biochem Biophys Res Commun 240 8–14 Occurrence Handle10.1006/bbrc.1997.7589 Occurrence Handle1:CAS:528:DyaK2sXnsVWjsLY%3D Occurrence Handle9367872

    Article  CAS  PubMed  Google Scholar 

  8. DE Jones Jr MD Brennan J Hempel R Lindahl (1988) ArticleTitleCloning and complete nucleotide sequence of a full-length cDNA encoding a catalytically functional tumor-associated aldehyde dehydrogenase. Proc Natl Acad Sci USA 85 1782–1786 Occurrence Handle1:STN:280:BieC2MfgslM%3D Occurrence Handle2831537

    CAS  PubMed  Google Scholar 

  9. A Kaiser M Fedrowitz U Ebert E Zimmermann HJ Hedrich et al. (2001) ArticleTitleAuditory and vestibular defects in the circling (ci2) rat mutant. Eur J Neurosci 14 1129–1142 Occurrence Handle10.1046/j.0953-816x.2001.01726.x Occurrence Handle1:STN:280:DC%2BD3MngvFCrtg%3D%3D Occurrence Handle11683905

    Article  CAS  PubMed  Google Scholar 

  10. H Koyama K Morishige N Takahashi JS Zanelli DN Fass et al. (1994) ArticleTitleMolecular cloning, functional expression and localization of a novel inward rectifier potassium channel in the rat brain. FEBS Lett 341 303–307 Occurrence Handle10.1016/0014-5793(94)80478-8 Occurrence Handle1:CAS:528:DyaK2cXkslKnsL4%3D Occurrence Handle8137958

    Article  CAS  PubMed  Google Scholar 

  11. Y Liang A Wang IA Belyantseva DW Anderson FJ Probst et al. (1999) ArticleTitleCharacterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2. Genomics 61 243–258 Occurrence Handle10.1006/geno.1999.5976 Occurrence Handle1:CAS:528:DyaK1MXntFWqsLo%3D Occurrence Handle10552926

    Article  CAS  PubMed  Google Scholar 

  12. S Lindemann A Lessenich U Ebert W Löscher (2001) ArticleTitleSpontaneous paroxysmal circling behavior in the ci2 rat mutant: epilepsy with rotational seizures or hyperkinetic movement disorder? Exp Neurol 172 437–445 Occurrence Handle10.1006/exnr.2001.7802 Occurrence Handle1:STN:280:DC%2BD3MnntFertg%3D%3D Occurrence Handle11716568

    Article  CAS  PubMed  Google Scholar 

  13. W Löscher A Richter G Nikkhah C Rosenthal U Ebert et al. (1996) ArticleTitleBehavioral and neurochemical dysfunction in the circling (ci) rat: a novel genetic animal model of a movement disorder. Neuroscience 74 1135–1142 Occurrence Handle10.1016/S0306-4522(96)00248-5 Occurrence Handle8895881

    Article  PubMed  Google Scholar 

  14. Y Matsuda S lnoue N Seki T Hosoi A Orimo et al. (1996) ArticleTitleChromosome mapping of human (ZNF179), mouse, and rat genes for brain finger protein (bfp), a member of the RING finger family. Genomics 33 325–327 Occurrence Handle10.1006/geno.1996.0203 Occurrence Handle1:CAS:528:DyaK28Xis1entrk%3D Occurrence Handle8660987

    Article  CAS  PubMed  Google Scholar 

  15. K Miyauchi R Masaki S Taketani A Yamamoto M Akayama (1991) ArticleTitleMolecular cloning, sequencing, and expression of cDNA for rat liver microsomal aldehyde dehydrogenase. J Biol Chem 266 19536–19542 Occurrence Handle1:CAS:528:DyaK38Xkt1WgsL4%3D Occurrence Handle1717467

    CAS  PubMed  Google Scholar 

  16. RJ Pennings H Kremer AF Deutman WJ Kimberling CW Cremers (2002) ArticleTitleFrom gene to disease; genetic causes of hearing loss and visual impairment sometimes accompanied by vestibular problems (Usher syndrome). Ned Tijdschr Geneeskd 146 2354–2358 Occurrence Handle1:STN:280:DC%2BD3s%2FgsFanug%3D%3D Occurrence Handle12510399

    CAS  PubMed  Google Scholar 

  17. FJ Probst RA Fridell Y Raphael TL Saunders A Wang et al. (1998) ArticleTitleCorrection of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280 1444–1447 Occurrence Handle10.1126/science.280.5368.1444 Occurrence Handle1:CAS:528:DyaK1cXjtlaku7Y%3D Occurrence Handle9603735

    Article  CAS  PubMed  Google Scholar 

  18. A Richter U Ebert JN Nobrega JJ Vallbacka M Fedrowitz et al. (1999) ArticleTitleImmunohistochemical and neurochemical studies on nigral and striatal functions in the circling (ci) rat, a genetic animal model with spontaneous rotational behavior. Neuroscience 89 461–471 Occurrence Handle10.1016/S0306-4522(98)00321-2 Occurrence Handle1:CAS:528:DyaK1MXnsVejug%3D%3D Occurrence Handle10077328

    Article  CAS  PubMed  Google Scholar 

  19. N Rozengurt I Lopez CS Chiu P Kofuji HA Lester et al. (2003) ArticleTitleTime course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit. Hear Res 177 71–80 Occurrence Handle10.1016/S0378-5955(02)00799-2 Occurrence Handle1:CAS:528:DC%2BD3sXhs1agsbo%3D Occurrence Handle12618319

    Article  CAS  PubMed  Google Scholar 

  20. G Van Camp PJ Coucke J Akita E Fransen S Abe et al. (2002) ArticleTitleA mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment. Hum Mutat 20 15–19 Occurrence Handle10.1002/humu.10096 Occurrence Handle1:CAS:528:DC%2BD38XlslKrtr0%3D Occurrence Handle12112653

    Article  CAS  PubMed  Google Scholar 

  21. A Wang Y Liang RA Fridell FJ Probst ER Wilcox et al. (1998) ArticleTitleAssociation of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science 280 1447–1451 Occurrence Handle10.1126/science.280.5368.1447 Occurrence Handle1:CAS:528:DyaK1cXjtlarsrs%3D Occurrence Handle9603736

    Article  CAS  PubMed  Google Scholar 

  22. Y Yuan M Shimura BA Hughes (2003) ArticleTitleRegulation of inwardly rectifying K+ channels in retinal pigment epithelial cells by intracellular pH. J Physiol Occurrence Handle10.1113/jphysiol.2002.033365 Occurrence Handle1:STN:280:DC%2BD3s%2FltlGjug%3D%3D Occurrence Handle12563001

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work is supported by the Deutsche Forschungsgemeinschaft (DFG/GK705). The authors also thank Ulrike Gänger and Sandra Przyklenk for their assistance in the genome-wide scan of the (LEW/Ztm-ci2 × BN/Ztm)F1 × LEW/Ztm-ci2 backcross, and Matthias Meyer for his assistance in the phenotypic characterization of the N2 animals.

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Authors and Affiliations

  1. Institute for Laboratory Animal Science, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

    Wojciech T. Chwalisz, Hans J. Hedrich & Dirk Wedekind

  2. Institute of Neuropathology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany

    Bernd U. Koelsch & Andrea Kindler-Röhrborn

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  1. Wojciech T. Chwalisz
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  2. Bernd U. Koelsch
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  3. Andrea Kindler-Röhrborn
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  4. Hans J. Hedrich
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  5. Dirk Wedekind
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Correspondence to Dirk Wedekind.

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Chwalisz, W.T., Koelsch, B.U., Kindler-Röhrborn, A. et al. The circling behavior of the deafblind LEW-ci2 rat is linked to a segment of RNO10 containing Myo15 and Kcnj12 . Mamm Genome 14, 620–627 (2003). https://doi.org/10.1007/s00335-003-3009-x

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  • DOI: https://doi.org/10.1007/s00335-003-3009-x

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