Phenotypic Mutation 'dan' (pdf version)
Allele | dan |
Mutation Type |
nonsense
|
Chromosome | 15 |
Coordinate | 100,933,505 bp (GRCm39) |
Base Change | A ⇒ T (forward strand) |
Gene |
Scn8a
|
Gene Name | sodium channel, voltage-gated, type VIII, alpha |
Synonym(s) | nmf335, nmf58, NMF335, C630029C19Rik, nur14, mnd2, seal, mnd-2, nmf2, med, ataxia 3, NaCh6, Nav1.6, motor end-plate disease |
Chromosomal Location |
100,767,739-100,943,819 bp (+) (GRCm39)
|
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with mental retardation, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010] PHENOTYPE: Spontaneous mutant homozygotes have ataxia, dystonia, muscular atrophy, progressive paralysis, Purkinje cell loss, in some cases severe head-tossing and for severe alleles, juvenile lethality. A mild, semidominant ENU allele causes deafness of variable penetrance and severity and mild tremor. [provided by MGI curators]
|
Accession Number | NCBI RefSeq: NM_001077499, NM_011323; MGI:103169
|
Mapped | Yes |
Amino Acid Change |
Lysine changed to Stop codon
|
Institutional Source | Beutler Lab |
Gene Model |
predicted gene model for protein(s):
[ENSMUSP00000080842]
[ENSMUSP00000104536]
[ENSMUSP00000104537]
[ENSMUSP00000104538]
[ENSMUSP00000144371]
[ENSMUSP00000144013]
|
AlphaFold |
no structure available at present |
SMART Domains |
Protein: ENSMUSP00000080842 Gene: ENSMUSG00000023033 AA Change: K1570*
Domain | Start | End | E-Value | Type |
Pfam:Ion_trans
|
131 |
422 |
7.4e-82 |
PFAM |
low complexity region
|
423 |
452 |
N/A |
INTRINSIC |
Pfam:Na_trans_cytopl
|
499 |
700 |
3.5e-72 |
PFAM |
low complexity region
|
701 |
712 |
N/A |
INTRINSIC |
Pfam:Ion_trans
|
750 |
985 |
2.2e-57 |
PFAM |
Pfam:Na_trans_assoc
|
989 |
1191 |
2e-59 |
PFAM |
Pfam:Ion_trans
|
1195 |
1472 |
6.2e-69 |
PFAM |
Pfam:Ion_trans
|
1519 |
1775 |
1.2e-56 |
PFAM |
IQ
|
1892 |
1914 |
1.2e-4 |
SMART |
low complexity region
|
1953 |
1972 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably null
|
SMART Domains |
Protein: ENSMUSP00000104536 Gene: ENSMUSG00000023033 AA Change: K1570*
Domain | Start | End | E-Value | Type |
Pfam:Ion_trans
|
72 |
322 |
1.9e-76 |
PFAM |
low complexity region
|
367 |
378 |
N/A |
INTRINSIC |
Pfam:Ion_trans
|
451 |
640 |
1.1e-47 |
PFAM |
Pfam:Na_trans_assoc
|
655 |
872 |
1.9e-71 |
PFAM |
Pfam:Ion_trans
|
898 |
1127 |
4.4e-59 |
PFAM |
PDB:1BYY|A
|
1129 |
1181 |
7e-30 |
PDB |
Pfam:Ion_trans
|
1220 |
1429 |
1.9e-51 |
PFAM |
Pfam:PKD_channel
|
1281 |
1436 |
5.6e-7 |
PFAM |
IQ
|
1558 |
1580 |
1.2e-4 |
SMART |
low complexity region
|
1619 |
1638 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably null
|
SMART Domains |
Protein: ENSMUSP00000104537 Gene: ENSMUSG00000023033 AA Change: K1580*
Domain | Start | End | E-Value | Type |
Pfam:Ion_trans
|
72 |
322 |
2.2e-76 |
PFAM |
low complexity region
|
335 |
364 |
N/A |
INTRINSIC |
Pfam:DUF3451
|
390 |
616 |
8.7e-70 |
PFAM |
Pfam:Ion_trans
|
697 |
886 |
1.3e-47 |
PFAM |
Pfam:Na_trans_assoc
|
901 |
1118 |
2.3e-71 |
PFAM |
Pfam:Ion_trans
|
1144 |
1186 |
9.7e-10 |
PFAM |
Pfam:Ion_trans
|
1182 |
1332 |
1.7e-31 |
PFAM |
PDB:1BYY|A
|
1334 |
1386 |
2e-29 |
PDB |
Pfam:Ion_trans
|
1425 |
1634 |
2.3e-51 |
PFAM |
Pfam:PKD_channel
|
1486 |
1641 |
6.6e-7 |
PFAM |
IQ
|
1763 |
1785 |
1.2e-4 |
SMART |
low complexity region
|
1824 |
1843 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably null
|
SMART Domains |
Protein: ENSMUSP00000104538 Gene: ENSMUSG00000023033 AA Change: K1570*
Domain | Start | End | E-Value | Type |
Pfam:Ion_trans
|
160 |
410 |
2.5e-76 |
PFAM |
low complexity region
|
423 |
452 |
N/A |
INTRINSIC |
Pfam:DUF3451
|
478 |
704 |
9.6e-70 |
PFAM |
Pfam:Ion_trans
|
785 |
974 |
1.4e-47 |
PFAM |
Pfam:Na_trans_assoc
|
989 |
1206 |
2.5e-71 |
PFAM |
Pfam:Ion_trans
|
1232 |
1461 |
5.7e-59 |
PFAM |
PDB:1BYY|A
|
1463 |
1515 |
4e-29 |
PDB |
Pfam:Ion_trans
|
1554 |
1763 |
2.5e-51 |
PFAM |
Pfam:PKD_channel
|
1615 |
1770 |
7.1e-7 |
PFAM |
IQ
|
1892 |
1914 |
1.2e-4 |
SMART |
low complexity region
|
1953 |
1972 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably null
|
SMART Domains |
Protein: ENSMUSP00000144371 Gene: ENSMUSG00000023033 AA Change: K1529*
Domain | Start | End | E-Value | Type |
Pfam:Ion_trans
|
131 |
422 |
4.1e-80 |
PFAM |
low complexity region
|
423 |
452 |
N/A |
INTRINSIC |
Pfam:Na_trans_cytopl
|
499 |
700 |
2.5e-69 |
PFAM |
low complexity region
|
701 |
712 |
N/A |
INTRINSIC |
Pfam:Ion_trans
|
750 |
985 |
1.2e-55 |
PFAM |
Pfam:Na_trans_assoc
|
989 |
1191 |
9.1e-57 |
PFAM |
Pfam:Ion_trans
|
1195 |
1274 |
7.6e-16 |
PFAM |
Pfam:Ion_trans
|
1270 |
1431 |
2.6e-33 |
PFAM |
Pfam:Ion_trans
|
1478 |
1734 |
6.5e-55 |
PFAM |
IQ
|
1851 |
1873 |
6e-7 |
SMART |
low complexity region
|
1912 |
1931 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably null
|
SMART Domains |
Protein: ENSMUSP00000144013 Gene: ENSMUSG00000023033 AA Change: K1570*
Domain | Start | End | E-Value | Type |
Pfam:Ion_trans
|
131 |
422 |
7.4e-82 |
PFAM |
low complexity region
|
423 |
452 |
N/A |
INTRINSIC |
Pfam:Na_trans_cytopl
|
499 |
700 |
3.5e-72 |
PFAM |
low complexity region
|
701 |
712 |
N/A |
INTRINSIC |
Pfam:Ion_trans
|
750 |
985 |
2.2e-57 |
PFAM |
Pfam:Na_trans_assoc
|
989 |
1191 |
2e-59 |
PFAM |
Pfam:Ion_trans
|
1195 |
1472 |
6.2e-69 |
PFAM |
Pfam:Ion_trans
|
1519 |
1775 |
1.2e-56 |
PFAM |
IQ
|
1892 |
1914 |
1.2e-4 |
SMART |
low complexity region
|
1953 |
1972 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably null
|
Meta Mutation Damage Score |
0.9755 |
Is this an essential gene? |
Probably essential (E-score: 0.790) |
Phenotypic Category |
Autosomal Recessive |
Candidate Explorer Status |
loading ... |
Single pedigree Linkage Analysis Data
|
|
Penetrance | |
Alleles Listed at MGI | All alleles(22) : Targeted(4) Gene trapped(3) Transgenic(1) Spontaneous(6) Chemically induced(8)
|
Lab Alleles |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00230:Scn8a
|
APN |
15 |
100853413 |
unclassified |
probably benign |
|
IGL00979:Scn8a
|
APN |
15 |
100853287 |
unclassified |
probably benign |
|
IGL01339:Scn8a
|
APN |
15 |
100930082 |
missense |
probably benign |
|
IGL01992:Scn8a
|
APN |
15 |
100866938 |
missense |
probably damaging |
1.00 |
IGL02215:Scn8a
|
APN |
15 |
100927453 |
splice site |
probably null |
|
IGL02311:Scn8a
|
APN |
15 |
100911164 |
missense |
probably damaging |
0.97 |
IGL02404:Scn8a
|
APN |
15 |
100937611 |
missense |
probably damaging |
1.00 |
IGL02652:Scn8a
|
APN |
15 |
100911357 |
missense |
probably damaging |
0.98 |
IGL02690:Scn8a
|
APN |
15 |
100868135 |
missense |
probably damaging |
1.00 |
IGL02704:Scn8a
|
APN |
15 |
100905943 |
missense |
possibly damaging |
0.94 |
IGL03084:Scn8a
|
APN |
15 |
100915053 |
missense |
probably damaging |
1.00 |
IGL03108:Scn8a
|
APN |
15 |
100872496 |
missense |
probably benign |
|
IGL03224:Scn8a
|
APN |
15 |
100933520 |
missense |
probably damaging |
1.00 |
nymph
|
UTSW |
15 |
100933527 |
missense |
probably damaging |
1.00 |
Tremord
|
UTSW |
15 |
100911385 |
missense |
probably damaging |
1.00 |
3-1:Scn8a
|
UTSW |
15 |
100937820 |
missense |
probably benign |
0.04 |
PIT4280001:Scn8a
|
UTSW |
15 |
100855370 |
missense |
probably damaging |
1.00 |
PIT4508001:Scn8a
|
UTSW |
15 |
100927573 |
missense |
probably damaging |
0.98 |
R0010:Scn8a
|
UTSW |
15 |
100911454 |
missense |
probably damaging |
1.00 |
R0010:Scn8a
|
UTSW |
15 |
100911454 |
missense |
probably damaging |
1.00 |
R0254:Scn8a
|
UTSW |
15 |
100916245 |
missense |
probably damaging |
1.00 |
R0412:Scn8a
|
UTSW |
15 |
100906187 |
splice site |
probably benign |
|
R0538:Scn8a
|
UTSW |
15 |
100933505 |
nonsense |
probably null |
|
R0539:Scn8a
|
UTSW |
15 |
100914449 |
missense |
probably damaging |
1.00 |
R0631:Scn8a
|
UTSW |
15 |
100933418 |
missense |
probably damaging |
1.00 |
R0726:Scn8a
|
UTSW |
15 |
100870711 |
missense |
probably damaging |
1.00 |
R0945:Scn8a
|
UTSW |
15 |
100913668 |
missense |
possibly damaging |
0.54 |
R0967:Scn8a
|
UTSW |
15 |
100933527 |
missense |
probably damaging |
1.00 |
R1164:Scn8a
|
UTSW |
15 |
100938043 |
missense |
probably benign |
0.06 |
R1283:Scn8a
|
UTSW |
15 |
100867052 |
missense |
possibly damaging |
0.82 |
R1368:Scn8a
|
UTSW |
15 |
100933422 |
missense |
probably damaging |
1.00 |
R1633:Scn8a
|
UTSW |
15 |
100927696 |
missense |
probably benign |
0.01 |
R1669:Scn8a
|
UTSW |
15 |
100909001 |
missense |
probably damaging |
1.00 |
R1694:Scn8a
|
UTSW |
15 |
100853409 |
nonsense |
probably null |
|
R1735:Scn8a
|
UTSW |
15 |
100913742 |
missense |
possibly damaging |
0.94 |
R1773:Scn8a
|
UTSW |
15 |
100937496 |
missense |
probably damaging |
0.97 |
R1940:Scn8a
|
UTSW |
15 |
100868085 |
missense |
probably benign |
0.22 |
R1996:Scn8a
|
UTSW |
15 |
100922260 |
missense |
probably damaging |
1.00 |
R2107:Scn8a
|
UTSW |
15 |
100916244 |
missense |
probably damaging |
0.99 |
R2251:Scn8a
|
UTSW |
15 |
100914987 |
missense |
probably benign |
0.02 |
R2516:Scn8a
|
UTSW |
15 |
100867043 |
missense |
probably benign |
0.05 |
R2917:Scn8a
|
UTSW |
15 |
100937613 |
missense |
probably damaging |
1.00 |
R3417:Scn8a
|
UTSW |
15 |
100869549 |
splice site |
probably benign |
|
R3896:Scn8a
|
UTSW |
15 |
100933379 |
missense |
probably benign |
|
R4024:Scn8a
|
UTSW |
15 |
100937674 |
missense |
probably damaging |
1.00 |
R4050:Scn8a
|
UTSW |
15 |
100911294 |
nonsense |
probably null |
|
R4193:Scn8a
|
UTSW |
15 |
100869484 |
missense |
probably damaging |
1.00 |
R4212:Scn8a
|
UTSW |
15 |
100854954 |
missense |
possibly damaging |
0.88 |
R4358:Scn8a
|
UTSW |
15 |
100838014 |
missense |
probably benign |
0.00 |
R4396:Scn8a
|
UTSW |
15 |
100870711 |
missense |
probably damaging |
1.00 |
R4428:Scn8a
|
UTSW |
15 |
100881784 |
missense |
probably damaging |
1.00 |
R4452:Scn8a
|
UTSW |
15 |
100854972 |
missense |
possibly damaging |
0.95 |
R4631:Scn8a
|
UTSW |
15 |
100914384 |
nonsense |
probably null |
|
R4693:Scn8a
|
UTSW |
15 |
100913572 |
missense |
probably damaging |
1.00 |
R4765:Scn8a
|
UTSW |
15 |
100938352 |
missense |
probably benign |
0.07 |
R4777:Scn8a
|
UTSW |
15 |
100913832 |
missense |
probably damaging |
1.00 |
R4949:Scn8a
|
UTSW |
15 |
100927663 |
missense |
probably damaging |
1.00 |
R4997:Scn8a
|
UTSW |
15 |
100854935 |
missense |
probably damaging |
1.00 |
R5246:Scn8a
|
UTSW |
15 |
100908938 |
missense |
probably damaging |
1.00 |
R5566:Scn8a
|
UTSW |
15 |
100872415 |
missense |
probably damaging |
1.00 |
R5875:Scn8a
|
UTSW |
15 |
100870703 |
nonsense |
probably null |
|
R6031:Scn8a
|
UTSW |
15 |
100881865 |
missense |
probably damaging |
1.00 |
R6031:Scn8a
|
UTSW |
15 |
100881865 |
missense |
probably damaging |
1.00 |
R6057:Scn8a
|
UTSW |
15 |
100872548 |
missense |
possibly damaging |
0.94 |
R6114:Scn8a
|
UTSW |
15 |
100938477 |
missense |
probably damaging |
0.99 |
R6362:Scn8a
|
UTSW |
15 |
100837996 |
splice site |
probably null |
|
R6535:Scn8a
|
UTSW |
15 |
100857588 |
intron |
probably benign |
|
R6677:Scn8a
|
UTSW |
15 |
100866953 |
missense |
probably damaging |
1.00 |
R6687:Scn8a
|
UTSW |
15 |
100872508 |
missense |
probably benign |
0.12 |
R6701:Scn8a
|
UTSW |
15 |
100937977 |
missense |
probably damaging |
1.00 |
R6719:Scn8a
|
UTSW |
15 |
100908896 |
critical splice acceptor site |
probably null |
|
R6739:Scn8a
|
UTSW |
15 |
100913836 |
missense |
possibly damaging |
0.82 |
R6769:Scn8a
|
UTSW |
15 |
100933445 |
missense |
probably benign |
|
R6786:Scn8a
|
UTSW |
15 |
100930096 |
missense |
probably benign |
0.00 |
R6849:Scn8a
|
UTSW |
15 |
100853468 |
splice site |
probably null |
|
R7108:Scn8a
|
UTSW |
15 |
100937659 |
missense |
probably benign |
0.01 |
R7215:Scn8a
|
UTSW |
15 |
100927711 |
missense |
possibly damaging |
0.80 |
R7217:Scn8a
|
UTSW |
15 |
100868108 |
missense |
probably benign |
0.00 |
R7219:Scn8a
|
UTSW |
15 |
100866984 |
missense |
probably damaging |
1.00 |
R7356:Scn8a
|
UTSW |
15 |
100855460 |
missense |
probably damaging |
1.00 |
R7479:Scn8a
|
UTSW |
15 |
100853358 |
missense |
probably damaging |
0.99 |
R7816:Scn8a
|
UTSW |
15 |
100908917 |
missense |
possibly damaging |
0.63 |
R7985:Scn8a
|
UTSW |
15 |
100914843 |
splice site |
probably null |
|
R8112:Scn8a
|
UTSW |
15 |
100927718 |
missense |
probably benign |
0.27 |
R8263:Scn8a
|
UTSW |
15 |
100881736 |
missense |
probably damaging |
1.00 |
R8305:Scn8a
|
UTSW |
15 |
100938387 |
missense |
probably benign |
0.01 |
R8489:Scn8a
|
UTSW |
15 |
100867014 |
missense |
probably damaging |
1.00 |
R8983:Scn8a
|
UTSW |
15 |
100900030 |
missense |
possibly damaging |
0.81 |
R9034:Scn8a
|
UTSW |
15 |
100927642 |
missense |
probably damaging |
0.98 |
R9050:Scn8a
|
UTSW |
15 |
100906161 |
missense |
possibly damaging |
0.80 |
R9240:Scn8a
|
UTSW |
15 |
100915068 |
nonsense |
probably null |
|
R9249:Scn8a
|
UTSW |
15 |
100914456 |
missense |
probably benign |
0.00 |
R9462:Scn8a
|
UTSW |
15 |
100930159 |
missense |
|
|
R9599:Scn8a
|
UTSW |
15 |
100911172 |
missense |
probably damaging |
1.00 |
R9609:Scn8a
|
UTSW |
15 |
100834407 |
missense |
possibly damaging |
0.91 |
R9653:Scn8a
|
UTSW |
15 |
100937947 |
missense |
probably damaging |
1.00 |
R9794:Scn8a
|
UTSW |
15 |
100933332 |
missense |
probably benign |
0.00 |
X0066:Scn8a
|
UTSW |
15 |
100937962 |
missense |
probably damaging |
1.00 |
X0066:Scn8a
|
UTSW |
15 |
100937961 |
missense |
probably damaging |
1.00 |
Z1176:Scn8a
|
UTSW |
15 |
100931399 |
missense |
probably damaging |
1.00 |
Z1177:Scn8a
|
UTSW |
15 |
100938103 |
missense |
probably benign |
0.00 |
|
Mode of Inheritance |
Autosomal Recessive |
Local Stock | Live Mice |
MMRRC Submission |
038240-MU
|
Last Updated |
2018-04-25 1:58 PM
by Anne Murray
|
Record Created |
2013-05-19 9:56 AM
by Jennifer Weatherly
|
Record Posted |
2014-03-28 |
Phenotypic Description |
Dan was identified as a visible mutant amongst N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice; the phenotype is characterized by the loss of the use of the hind legs (Figure 1).
|
Nature of Mutation | Whole exome HiSeq sequencing of the G1 grandsire identified 129 mutations. Four G3 mice with the dan phenotype and 22 unaffected mice from a single pedigree were genotyped at all mutation sites. Three mutations (in Rapgef3, Slc11a2, and Scn8a) on chromosome 15 were homozygous in all four of the dan mice and either heterozygous (n = 12) or wild-type (n = 10) in the unaffected mice (-log10[p(non-linkage)] = 5.922). The dan phenotype resembles that of other Scn8a mutant mice (described in the “Putative Mechanism” section, below), indicating that the mutation in Scn8a is causative. The Scn8a mutation is an A to T transversion at base pair 101,035,624 (v38) on Chromosome 15, or base pair 165,802 in the GenBank genomic region NC_000081 encoding Scn8a. The mutation corresponds to residue 4861 in the mRNA sequence NM_001077499 (isoform 1) within exon 26 of 27 total exons and residue 4762 in the mRNA sequence NM_011323 (isoform 2) within exon 25 of 26 total exons. 165787 TGCGAGTGTGTGCTCAAAATGTTTGCCTTGAGA
1565 -C--E--C--V--L--K--M--F--A--L--R- Genomic numbering is shown, corresponding to NC_000081. The mutated nucleotide is indicated in red. The mutation results in substitution of a lysine (K) for a premature stop codon (*) at amino acid 1570 in both isoforms of the SCN8A sodium channel.
|
Illustration of Mutations in
Gene & Protein |
|
---|
Protein Prediction |
Scn8a encodes the voltage-gated sodium channel SCN8A (alternatively, Nav1.6). Nav1.6 contains four homologous domains (I-IV) that each consist of six transmembrane α-helices (S1-S6) (1;2). The S4 helices constitute the voltage sensors of the channel. A membrane reentrant extracellular loop (i.e., the pore loop) is located between S5 and S6 in each of the four domains and lines the extracellular, narrow entrance to the pore (3;4). The S5 and S6 helices line the intracellular, wider exit of the pore, while amino acids (F1752 and Y1759) in in the S6 helix contribute to drug binding (5;6). The dan mutation (K1570*) is within the S2 helix of domain IV (Figure 2). Protein and mRNA expression have not been examined. For more information about Scn8a, please see the record for TremorD.
|
Putative Mechanism | Mutations in Scn8a (e.g., Scn8amed, MGI:1856078; Scn8amed-tg, MGI:1856414; Scn8amed-J, MGI:1856079) lead to a range of neurological disorders in mice such as tremor, ataxia, early-onset progressive paralysis of the hind limbs, severe muscle atrophy, degeneration of Purkinje cells, and juvenile lethality (7). Loss of Scn8a expression in Scn8amed homozygous mice resulted in reduced conduction velocity of the sciatic nerve between postnatal day 17 and 23 and subsequent failure of transmission at the neuromuscular junction and muscle denervation (8-10); these defects may underlie the hindlimb paralysis observed in these and dan homozygous mice. The dan mutation may result in degradation of the Scn8a mRNA by nonsense-mediated decay; translated protein may be truncated and lack helices S3-S6 and the pore loop of domain IV as well as the cytoplasmic C-terminal tail.
|
Primers |
PCR Primer
dan_pcr_F: TTCGTCACGCAACAAGCCTTCG
dan_pcr_R: GCTCTCAGAAATCTGGTCCTCACAC
Sequencing Primer
dan_seq_F: ACAAGCCTTCGACATCGTG
dan_seq_R: TCCTCACACCTGGGGTC
|
Genotyping | Dan genotyping is performed by amplifying the region containing the mutation using PCR followed by sequencing of the amplified region to detect the nucleotide change. The following primers were used for PCR amplification: Primers for PCR amplification
Dan(F): 5’- TTCGTCACGCAACAAGCCTTCG-3’
Dan(R): 5’- GCTCTCAGAAATCTGGTCCTCACAC-3’ Primers for sequencing
Dan(F): 5’- ACAAGCCTTCGACATCGTG-3’
Dan(R): 5’-TCCTCACACCTGGGGTC-3’ PCR program
1) 94° C 2:00
2) 94° C 0:30
3) 57° C 0:30
4) 72° C 1:00
5) repeat steps (2-4) 29x
6) 72° C 7:00
7) 4° C hold The following sequence of 418 nucleotides (from Genbank genomic region: NC_000081 of the linear genomic sequence of Scn8a) is amplified: 165640 t tcgtcacgca acaagccttc
165661 gacatcgtga tcatgatgct tatctgcctt aacatggtga ccatgatggt ggagacagac
165721 acacagagca agcagatgga gaacattctc tactggatta atctggtctt cgtcatcttc
165781 ttcacctgcg agtgtgtgct caaaatgttt gccttgagac actactattt caccattggc
165841 tggaacatct ttgactttgt ggtggtcatt ctctccattg tgggtgagtg ggtgcagcca
165901 caggaagggg ggtgagtggg cggggccaca ggaagggtga gtgggcgggg ccacaggaag
165961 agggggtgag tgggcggggc cacgggaaga ggggatgagt gggcggggcc acaggaagga
166021 ccaggacccc aggtgtgagg accagatttc tgagagc PCR primer binding sites are underlined; Sequencing primer binding sites are highlighted; the mutated nucleotide is in red.
|
References | 1. Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., and Meisler, M. H. (1995) Mutation of a New Sodium Channel Gene, Scn8a, in the Mouse Mutant 'Motor Endplate Disease'. Nat Genet. 10, 461-465.
2. Schaller, K. L., Krzemien, D. M., Yarowsky, P. J., Krueger, B. K., and Caldwell, J. H. (1995) A Novel, Abundant Sodium Channel Expressed in Neurons and Glia. J Neurosci. 15, 3231-3242.
5. Ragsdale, D. S., McPhee, J. C., Scheuer, T., and Catterall, W. A. (1996) Common Molecular Determinants of Local Anesthetic, Antiarrhythmic, and Anticonvulsant Block of Voltage-Gated Na+ Channels. Proc Natl Acad Sci U S A. 93, 9270-9275.
7. Noujaim, S. F., Kaur, K., Milstein, M., Jones, J. M., Furspan, P., Jiang, D., Auerbach, D. S., Herron, T., Meisler, M. H., and Jalife, J. (2012) A Null Mutation of the Neuronal Sodium Channel NaV1.6 Disrupts Action Potential Propagation and Excitation-Contraction Coupling in the Mouse Heart. FASEB J. 26, 63-72.
8. Kearney, J. A., Buchner, D. A., De Haan, G., Adamska, M., Levin, S. I., Furay, A. R., Albin, R. L., Jones, J. M., Montal, M., Stevens, M. J., Sprunger, L. K., and Meisler, M. H. (2002) Molecular and Pathological Effects of a Modifier Gene on Deficiency of the Sodium Channel Scn8a (Na(v)1.6). Hum Mol Genet. 11, 2765-2775.
|
Science Writers | Anne Murray |
Illustrators | Diantha La Vine, Peter Jurek |
Authors | Jennifer Weatherly
Tiana Purrington |