These mice carry the spontaneous Snell's waltzer mutation ( Myo6sv ) characterized by circling, head-tossing, deafness, and hyperactivity. The Snell's waltzer mutation is maintained in repulsion with the closely linked short ear mutation (Bmpse), both located on Chromosome 9, on the stock that is homozygous for chinchilla (Tyrc-ch).Read More +
Mice homozygous for the Snell's waltzer spontaneous mutation (Myo6sv) show to a marked degree the typical circling, head-tossing, deafness, and hyperactivity of other mutant mice of this type. Homozygous mutant mice are recognizable by the age of 1 week. The abnormalities of the inner ear consist of degeneration of the entire neuroepithelium comprising the organ of Corti, the saccular and utricular maculae, and the cristae of all three semicircular canals. Although viability of homozygotes is nearly normal, breeding ability is reduced and males are more reliable breeders than females.
Specific cytoskeletal components are critical for specific cellular structures. The microvilli of intestinal brush border cells in Myo6sv homozygotes are shorter than normal. While myosin 6 is not critical for the development of hair cell stereocilia, it is essential for their maintenance. At birth the stereocilia appear nearly normal with only occasional stereocilia showing early signs of fusion at their bases, but by 3 days of age most hair cells appear disorganized with full fusing of steriocilia. Continued degeneration yields giant stereocilia by 20 days of age and degeneration of the inner and outer hair cells in the organ of Corti by 6 weeks of age. Reissner's membrane, the stria vascularis, and the spiral ganglion appear normal. At 20 or 30 days of age, direct cochlear stimulation failed to elicit a compound action potential or cochlear microphonic response indicating deafness in Myo6sv homozygotes. A mutation in human MYO6 has been associated with a nonsyndromic dominant form of deafness. (Deol and Green, 1966; Avraham et al., 1995; Self et al., 1999; Melchoinda et al., 2001; Buss et al., 2001.)
Although myosin 6 co-localization with clatherin-coated pits suggests a role in endocytosis, Self et al. reported uptake of the membrane dye FM1-43 by hair cells of 1 and 3 day old Myo6sv mutant mice indicating that endocytosis by hair cells does not require MYO6. Fibroblast cell lines from mice homozygous for the Myo6sv mutation have a 40% reduction in the level of trans-Golgi network secretion to the plasma membrane paralleling a 40% reduction in Golgi volume. Additionally, the mutant Golgi complexes are smaller and more fragmented than normal. Transfection of fibroblasts from Myo6sv homozygotes with full length myosin 6 returns the Golgi morphology and secretion to normal. (Self et al., 1999; Warner et al., 2003.) In addition to cochlear defects, homozygous mice exhibit a significant reduction in the amplitude of a and b waves as measured by electroretinogram, although there is no photoreceptor cell loss. (Kitamoto et al., 2005)
The Snell's waltzer mutation is maintained in repulsion with the closely linked short ear mutation (Bmpse), both located on Chromosome 9.
The chinchilla (Tyrc-ch) mutation arose spontaneously in the 1920's (Feldman H. W. 1922 Am. Nat. 56:573-574). Short ear (Bmp5se) arose spontaneously in mice obtained from a commercial breeder about 1921 (Lynch C.H. 1921 Am. Nat. 55:421-426). The Snell's waltzer (Myo6sv) mutation was found in the B10.HA(33NX) stock of Dr. G.D. Snell at the Jackson Laboratory in the late 1950s. In 1959 an Myo6sv/Myo6sv mouse was crossed to the SEC/1 strain of Dr. M. C. Green. The genotype of SEC/1 was a/a Tyrp1b/Tyrp1b Tyrc-ch/Tyrc-ch Bmp5se/+. A very close linkage was found between Bmp5se and Myo6sv and the two loci were maintained in repulsion. The stock was inbred as Tyrc-ch/Tyrc-ch Bmp5se +/+ Myo6sv and was cryopreserved in 1983 by crossing C57BL/6J females to Tyrc-ch/Tyrc-ch Bmp5se +/+ Myo6sv at F67 to generate embryos.
|Allele Name||Snell's waltzer|
|Gene Symbol and Name||Myo6, myosin VI|
|Strain of Origin||B10.HA/(33NX)Sn|
|Molecular Note||On the basis of a series of southern blots, this mutation appears to involve a 1.1 kb intragenic deletion. Gene transcripts could be detected by RT-PCR. Sequence analysis of these transcripts identified a 150 bp deletion corresponding to nucleotides 2456-2585. The deletion results in a frame shift which introduces a stop codon at the beginning of the neck region.|
|Allele Synonym(s)||cch; cr|
|Gene Symbol and Name||Tyr, tyrosinase|
|Strain of Origin||fancier's stock|
|Molecular Note||The mutation in the chinchilla allele was found to be a G-to-A point mutation that results in an amino acid change at position 482 or 464 from alanine to threonine (p.A482T for pre-protein, p.A464T for mature protein).|
|Allele Name||short ear|
|Gene Symbol and Name||Bmp5, bone morphogenetic protein 5|
|Strain of Origin||mice from Abbie Lathrop mouse farm|
|General Note||Phenotypic Similarity to Human Syndrome: Ear, Patella, Short Stature Syndrome (Meier-Gorlin Syndrome) in homozygous mice (J:24474)|
|Molecular Note||The C to T substitution creates a stop codon at arginine codon 208 (p.R208*). The resulting truncated protein does not include the carboxy terminal signaling portion of the molecule.|
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