V/LeJ

Stock number: 000275
Research areas: Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

This inbred mutant strain carries the nonagouti (a), fuzzy (fz), leaden (Mlph^ln), and piebald (Ednrb^s) mutations, and is segregating for the waltzer (Cdh23^v) neurological mutation.

Detailed description

This strain was originally used as a linkage stock for gene mapping. It is homozygous for several visible recessive mutations all located on different chromosomes including nonagouti (a), fuzzy (fz), leaden (Mlph^ln), and piebald (Ednrb^s) and is segregating for the neurological mutation, waltzer (Cdh23^v). Homozygous waltzer mice show the circling, head-tossing, deafness, and hyperactivity typical of the circling mutants. Abnormalities of the inner ear include degeneration of the organ of Corti, spiral ganglion, stria vascularis, and saccular macula. Homozygous piebald mice show irregular white spotting, the amount of which is greatly influenced by minor modifying genes. Homozygous piebald mice have dark eyes. The white areas of the coat are completely lacking in melanocytes and there is a reduction in the number of melanocytes in the choroid layer of the eye.

Development

The waltzing mutation came from the Japanese mouse fanciers and was received by George Snell at The Jackson Laboratory from Ludwin in 1947 when the stock was homozygous for nonagouti, leaden, waved 1, and piebald. This stock was crossed once to C57BL/10 and non-sibling mated for approximately 22 generations after which it was crossed to a C57BL/10 stock bearing fuzzy and jittery. The fuzzy and waved 1 mutations were selectively bred out of the stock. Sibling inbreeding of this stock began in approximately 1960. In 1983 this stock was at generation F47 and waltzer heterozygous females were bred with homozygous males to generate embryos for cryopreservation.

Allele

Symbol: Cdh23^v
Name: waltzer
MGI accession ID: MGI:1856228
Generation method: Spontaneous
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Chromosome: 10
Strain of origin: old mutant of the mouse fancy
Molecular note: A single G nucleotide insertion at coding nucleotide 834 causes a frameshift and premature termination of the encoded protein.
General note: Viability and breeding ability are somewhat less than normal. Homozygotes show the typical circling, head-tossing, deafness, and hyperactivity of the circling mutants. Most of them are deaf from the beginning. Abnormalities of the inner ear include degeneration of the organ of Corti, spiral ganglion, stria vascularis, and saccular macula. Double heterozygotes with shaker-1 (Cdh23^v/+ Myo7^ash1/+) are deaf beginning at 3 to 6 months. They have changes similar to those of the homozygotes in the organ of Corti, stria vascularis, and spiral ganglion, but less severe and with much later onset (J:13130)(J:15164).

Allele

Symbol: Ednrb^s
Name: piebald
MGI accession ID: MGI:1856148
Generation method: Spontaneous
Marker symbol: Ednrb
Marker name: endothelin receptor type B
Chromosome: 14
Strain of origin: old mutant of the mouse fancy
Molecular note: This mutation is allelic to a targeted mutation for this gene. Homozygous mice produce approximately 25% of the normal levels of transcript from this allele. RT-PCR analysis demonstrated that no alterations in the coding sequence would result in any alteration of the amino acid sequence. A 5.5 kb retrotransposon-like element is found in intron 1. About 75% of the mRNA produced is an aberrant 6.5 kb form lacking exons 2-6 but containing exon 1. The remaining 25% of the mRNA formed is of normal, 4.4 kb, size.
General note: Also called piebald spotting. This is a very old mutation of the mouse fancy, and was described in the scientific literature as early as 1920 (J23183). Some piebalds in existing stocks may be of independent origin.

Allele

Symbol: Mlph^ln
Name: leaden
MGI accession ID: MGI:1856674
Generation method: Spontaneous
Marker symbol: Mlph
Marker name: melanophilin
Chromosome: 1
Strain of origin: C57BR
Molecular note: This allele has a C-to-T transition at mRNA nucleotide position 266. This introduces a stop codon at arginine codon 31 (p.R31*) in the sequence of the normally spliced transcript and it also creates a new G-GT splice donor site in exon 2. Use of this alternative splice site yields a transcript with an in-frame 21 base pair deletion that deletes 7 amino acids from the translated protein. Northern blots failed to detect this size difference and did not find any change from normal in transcript expression level. Sequence analysis failed to detect any wild-type transcripts.

Allele

Symbol: Sgk3^fz
Name: fuzzy
MGI accession ID: MGI:1856038
Generation method: Spontaneous
Marker symbol: Sgk3
Marker name: serum/glucocorticoid regulated kinase 3
Chromosome: 1
Strain of origin: CFW stock
Molecular note: This mutation comprises insertion of a single adenine following nucleotide 579 of the cDNA sequence, in a region encoded by exon 10 of the gene, that causes a shift in the amino acid reading frame and premature termination of protein translation following leucine 192 (Leu192Ter), which resides in the serine/threonine kinase domain.