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|Coordinate||75,211,127 bp (GRCm38)|
|Base Change||C ⇒ T (forward strand)|
|Gene Name||myosin VA|
|Synonym(s)||9630007J19Rik, Dbv, flail, MVa, Myo5, MyoVA|
|Chromosomal Location||75,071,015-75,223,688 bp (+)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is one of three myosin V heavy-chain genes, belonging to the myosin gene superfamily. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. The protein encoded by this gene is abundant in melanocytes and nerve cells. Mutations in this gene cause Griscelli syndrome type-1 (GS1), Griscelli syndrome type-3 (GS3) and neuroectodermal melanolysosomal disease, or Elejalde disease. Multiple alternatively spliced transcript variants encoding different isoforms have been reported, but the full-length nature of some variants has not been determined. [provided by RefSeq, Dec 2008]
PHENOTYPE: Mutations in this gene result in diluted coat color, behavioral deficits including opisthotonus, and postnatal or premature death. [provided by MGI curators]
|Amino Acid Change||Glutamine changed to Stop codon|
|Institutional Source||Beutler Lab|
Q1610* in Ensembl: ENSMUSP00000116028 (fasta)
|Gene Model||not available|
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Embryos, Sperm, gDNA|
|Last Updated||2018-05-22 9:40 AM by Anne Murray|
The silver decerebrate 2 phenotype was identified among ENU-induced G3 mice, and is identical to that of silver decerebrate. Homozygous mutants exhibit defects in both coat color and behavior. The fur, ears, feet and tail of homozygotes are dark gray. Several behavioral phenotypes are distinct in supine versus prone positions. When placed in a supine position, silver decerebrate 2 mutants exhibit opisthotonus (a convulsive arching of the head and neck), abrupt movements of the feet, and have difficulty righting themselves. In the normal prone position, mutants extend all four feet caudally. In either circumstance, all of the digits are splayed. Homozygous silver decerebrate 2 mice die at approximately three weeks of age. A similar spectrum of phenotypes is observed in dilute lethal and dilute opisthotonus mutants, which contain mutations in the Myo5a gene (1).
|Nature of Mutation|
The mutated nucleotide is indicated in red lettering, and changes the codon for glutamine 1610 to a stop codon (Figure 1).
Please see the record for new gray for information about Myo5a.
The silver decerebrate 2 mutation truncates the C-terminal 243 amino acids of myosin Va, which encodes part of the globular tail domain (GTD). The GTD both mediates binding to specific organelles, such as melanosomes (2;3), and serves as a negative regulator of motor activity by folding back and contacting residues in the head domain (4). Point mutations in the GTD abolish the ability of the GTD to inhibit motor activity and prevent folding of myosin Va into the inhibitory conformation (5), although the physiological consequences of such mutations are unknown. Interestingly, other alleles of Myo5a resulting in early postnatal death are null alleles (1;6;7). The silver decerebrate 2 mutation is predicted to abrogate the function of the GTD. Its similar phenotype to that of Myo5a null alleles suggests that the mutation quite fully and severely inhibits the function of myosin Va, and thus that the GTD is critical to normal myosin Va function. It remains possible that the silver decerebrate 2 mutation destabilizes the protein and leads to its degradation.
|Primers||Primers cannot be located by automatic search.|
Silver decerebrate 2 genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide change.
Primers for PCR amplification
SD2(F): 5’-ATTGAGAATAGTGACCCTGGCACGAGGTAG -3’
SD2(R): 5’-CTTTAGAGAGGAAGTCAACACGGATCCCAG -3’
1) 94°C 3:00
2) 94°C 0:30
3) 60°C 0:30
4) 68°C 0:50
5) repeat steps (2-4) 35X
6) 68°C 3:00
7) 4°C ∞
Primers for sequencing
SD2_seq(F): 5’- CTGGCACGAGGTAGAAGGGATGAG -3’
SD2_seq(R): 5’- AGTCAACACGGATCCCAGTGCTTCAGAC -3’
The following sequence of 428 nucleotides (from Genbank genomic region NC_000075 for linear DNA sequence of Myo5α) is amplified:
139705 attgag aatagtgacc ctggcacgag gtagaaggga
139741 tgagcaggat gcagagtgag gcagacagag acattggctt cctgtgcacc actaacattg
139801 tgttgattct agggctttat gaagcacaac acgtctcgcc agaatgagca ctgcctcacc
139861 aattttgacc ttgctgaata tcggcaagta ctgagtgact tggccattca gatctatcag
139921 cagcttgtga gggtgttaga gaacattctt cagccaatga taggtaagac cagtgtcgct
139981 gagcatcatg ggtgcttgct gacaaatgag gtcagtggta cgtacgtgtg acaggcatga
140041 gttcatgtgg agaacataaa gcggtaactg cgacagaagt caggctccac gtgtctgaag
140101 cactgggatc cgtgttgact tcctctctaa ag
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated T is shown in red text.
1. Searle, A. G. (1952) A lethal allele of dilute in the house mouse, Heredity 6, 395-401.
2. Wu, X. S., Rao, K., Zhang, H., Wang, F., Sellers, J. R., Matesic, L. E., Copeland, N. G., Jenkins, N. A., and Hammer, J. A., III (2002) Identification of an organelle receptor for myosin-Va, Nat. Cell Biol. 4, 271-278.
3. Fukuda, M. and Kuroda, T. S. (2004) Missense mutations in the globular tail of myosin-Va in dilute mice partially impair binding of Slac2-a/melanophilin, J. Cell Sci. 117, 583-591.
4. Wang, F., Thirumurugan, K., Stafford, W. F., Hammer, J. A., III, Knight, P. J., and Sellers, J. R. (2004) Regulated conformation of myosin V, J. Biol. Chem. 279, 2333-2336.
5. Li, X. D., Jung, H. S., Wang, Q., Ikebe, R., Craig, R., and Ikebe, M. (2008) The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va, Proc. Natl. Acad. Sci. U. S. A 105, 1140-1145.
6. Moore, K. J., Seperack, P. K., Strobel, M. C., Swing, D. A., Copeland, N. G., and Jenkins, N. A. (1988) Dilute suppressor dsu acts semidominantly to suppress the coat color phenotype of a deletion mutation, dl20J, of the murine dilute locus, Proc. Natl. Acad. Sci. U. S. A 85, 8131-8135.
|Science Writers||Eva Marie Y. Moresco|
|Illustrators||Diantha La Vine|
|Authors||Sophie Rutschmann, Celine Eidenschenk, Bruce Beutler|
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