260 Mammalian Genome 9, Brief Data Report gated potassium channels associate with the transmembrane alpha Genetic mapping of the voltage-gated shaker subunits to modulate channel activity and inactivation kinetics. potassium channel beta subunit Kcnabl to The Kv[31 cDNA has been isolated from human, rat, and mouse mouse Chromosome 3 [5-7]. Alternative splicing of the N-terminus of the human gene, KCNAIB, generates the three beta subunit isoforms Kvl3la, Kv(3lb, and Kv(33 . The assignment of human KCNAIB to Chr J.M. Jones,' E. Bentley, 2 M.H. Meisler, l 3q26.1  indicated that the mouse ortholog was likely to be Susan M. Darling 2 located either in the conserved linkage group on central Chr 6, or in the conserved linkage group on proximal Chr 3. Analysis of the 'Department of Human Genetics, University of Michigan, mnd2 backcross for segregation of Kcnabl demonstrated lack of Ann Arbor, Michigan 48109-0618, USA 2Department of Anatomy and Developmental Biology, University linkage with previously typed markers on Chr 6. We detected College London, Gower Street, London WC1E 6BT, UK linkage by typing the mnd2 backcross for the Chr 3 markers D3Mit22, 186, 93, and 167. Higher resolution localization of Kc- Received: 1 September 1997 / Accepted: 19 November 1997 nab] on Chr 3 was obtained by analysis of the my backcross (Fig. 1). Kcnabl is located approximately 31 cM distal to the centro- Mus musculus Species: mere and 17 cM proximal to a cluster of potassium channel alpha Locus name: Potassium voltage-gated channel, shaker-related subunits . Kcnabl was eliminated as a candidate for the my subfamily, beta subunit 1 mutation by the observation of several recombinants (data not Locus symbol: Kcnabl shown). Mutations in alpha subunits of voltage-gated ion channels Chromosome (Chr) 3: Cen-I12 (D3Nds6)-7.5 ± Map position: have been associated with several human neurological disorders 2.2-D3Nds38, D3Mit69, D3Mit172, D3Mit335-4.8 ± 1.8-Kcnabl, and with the mouse mutants motor endplate disease  and tot- D3Mit228-0.7 ± 0.7-D3Mit241-1.4 ± 1.0-D3Mit277-0.7 ± 0.7- tering . A mutation in the beta 4 subunit of the voltage-gated D3Mit121, D3Mit209-13.6 ± 2.8-Tshb (D3Nds8)-3.4 ± 1.5- calcium channel was recently identified in the mouse mutant le- D3Mit104-11.0 ± 2.6-Adhl (D3Nds9). thargic, a model of ataxia and epilepsy [111. Mutations in the Method of mapping: Linkage was initially identified by the low potassium channel beta 1 subunit Kcnab] may also play a role in D3Mit22 (0/22), rate of recombination of Kcnabl with the markers inherited neurological disease. D3Mitl86 (0/22), D3Mit93 (3/22), and D3Mit167 (3/22) in the interspecific backcross [(C57BL/6J-mnd2/+ x CAST/Ei) x Acknowledgments: We thank Dr. Kenneth McCormack for the gift of the C57BL/6J-mnd2/+] . Higher resolution mapping was obtained Kcnabl cDNA clone and Drs. Albee Messing and Barry Ganetzky for by typing 146 N 2 progeny of the intersubspecific backcross panel helpful advice. This work was supported by the Wellcome Trust (Grant No. [(CAST/Ei x NMRI-my/my) x NMRI- my/my] segregating the my- 050619) and the USPHS (GM24872). elencephalic blebs mutation on Chr 3 . Locus order and genetic distance were determined with Map Manager v. 2.6.5 N. References Database deposit information: MGD accession number MGD- 1. Jones JM, Albin RL, Feldman EL, Simin K, Schuster TG, Dunnick JNUM-42328 WA, Collins JT, Chrisp CE, Taylor BA, Meisler MH (1993) Genomics Molecular reagents used for mapping: A 1.4-kb cDNA mouse 16, 669-677 clone containing the entire 1.2-kb open reading frame [4,5] was 2. Bentley E, Guenet JL, Gossler A, Darling SM Manuscript in prepa- generated by PCR amplification of mouse brain RNA by Kenneth ration McCormack (University of Wisconsin, Madison). 3. Manly KF (1993) Mamm Genome 4, 303-313 RFLPs were typed by Southern blotting of Allele detection: Two 4. Schultz D, Litt M, Smith L, Thayer M, McCormack K (1996) Genom- genomic DNA: a TaqI polymorphism segregating in the mnd2 ics 31, 389-391 backcross with unique fragments of 3.6 kb in CAST/Ei and 3.3 kb 5. McCormack K, McCormack T, Tanouye M, Rudy B, Stuhmer W in C57BL/6J, and a Pstl polymorphism segregating in the my (1995) FEBS Lett 370, 32-36 backcross with unique fragments of 2.6 and 4.5 kb in CAST/Ei and 6. Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN, Dolly JO, 2.3 kb in NMRI. Microsatellite reference markers were scored as Pongs 0 (1994) Nature 369, 289-294 described . 7. Fink M, Duprat F, Lesage F, Heurteaux C, Romey G, Barhanin J, Previously identified homolog: The human homolog KCNAIB Lazdunski M (1996) J Biol Chem 271, 26341-26348 was mapped to Chr 3q26.1 by FISH . 8. Yui MA, Wakeland EK (1997) Mamm Genome 7 (Suppl), S45-S59 Discussion: Voltage-gated potassium channels of the shaker fam- 9. Burgess DL, Kohrman DC, Galt J, Plummer NW, Jones JM, Spear B, ily contribute to the generation of action potentials in nerve and Meisler MH (1995) Nat Genet 10, 461-465 muscle and are involved in hormone secretion and other functions Fletcher CF, Lutz CM, O'Sullivan TN, Shaughnessy JD Jr, Hawkes R, in nonexcitable cell types. Cytoplasmic beta subunits of voltage- Frankel WN, Copeland NG, Jenkins NA (1996) Cell 87, 607-617 11. Burgess DL, Jones JM, Meisler MH, Noebels JL (1997) Cell 88, 385-392 Correspondence to: S.M. Darling Fig. 1. Localization of Kcnabl on mouse Chr 3. Haplotype analysis of 146 progeny derived from a . Q . q n q n q Q n q n q Q q backcross segregating the ed to cephalic blebs D3Nds6 (112) IOU mutati mutation showing howing loci linked to Kcnab] on Chr r 3. 1- 7.5 2.2 D3Nds38, D3Mu69, 172. 335 q q Empty boxes represent CAST/Ei alleles; filled U U Q U q q U Q U q l D q U q 1.8 Kcnab1, D3Mit228 Q q boxes represent NMRI alleles. Loci are listed in n Q DO Q 1001010 0.7 +0 7 order with the most proximal at the top. Genetic D3Mir241 $ q q 1 Q U q Q Q • q U q $ q q $ q 1.4 1.0 order was WMW77 0 qq MQNQN q NQNQ U qq 1- 07+0.7 of observed recombinants. eecomb Kcnabl nwas scored as D3Mirl21. 209 $ Q q U q U Q I ID I q U q q • O r 13.6 2.8 described in the text; all other scorings we were as a D3Nds8 (Tshb) U q U q I I q U I q U q q 100 U U r 3.4 I.5 ± described . Numbers for each class of haplotype ere as D3Mrr104 Q Q r, U q U q U U DUDU U DDUI I 1 + 2.6 are indicated below the haplotype. Intennarker D3Nds9(Adhi) 00000N0NO00010$0 q Q distance (cM ± SE) is indicated to the right of the 29 57 5 4 I 6 I 1 19 11 14 7 6 I 1 1 figure.
Mammalian Genome – Springer Journals
Published: Mar 21, 2009
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