B6C3Fe-a/a Hoxa13^Hd Mcoln3^Va-J/J

Stock number: 000296
Research areas: Dermatology Research, Developmental Biology Research, Neurobiology Research, Sensorineural Research

Detailed description

Mice heterozygous for the varitint-waddler Jackson spontaneous mutation (Mcoln3^Va-J) are more pigmented than the original varitint waddler mice (Mcoln3^Va) and behave normally although they are deaf. They have slightly diluted coat color, a large irregular belly spot, and white feet and tail tip. Homozygous mutant mice have extensive white spotting interspersed with patches of diluted color. They are deaf but behave normally and are fertile. Compound heterozygotes of the two alleles (Mcoln3^Va-J/Mcoln3^Va) are similar to Mcoln3^Va-J/Mcoln3^Va-J mice but are smaller with more white spotting and abnormal behavior. They are deaf and circle vigorously. Viability and fertility of Mcoln3^Va-J/Mcoln3^Va mice are considerably reduced. This strain is also carrying the semidominant hypodactyly spontaneous mutation (Hoxa13^Hd). Heterozygous hypodactyly mutant mice are viable and fertile. Heterozygotes are missing the terminal phalanx of the first digit of the hindfoot and show variable penetrance for shortening or missing first phalanx. The forefeet are normal. Homozygous mutant mice have a single digit on each foot and greatly reduced carpals, metacarpals, tarsals, and metatarsals. The surviving digit is probably the fifth. Most homozygotes die before birth, but a few have survived to maturity but are sterile.

Development

The mutation hypodactyly (Hoxa13^Hd) arose spontaneously in strain MYA/Hu of Dr. K. P. Hummel at The Jackson Laboratory in approximately 1965. It was backcrossed onto a hybrid of C3HeB/Hu x DBAfB/Hu for 5 generations before being backcrossed onto C57BL/6J for 7 generations. The mutation Mcoln3^Va-J arose spontaneously in a chromosome 3 linkage testing stock and was backcrossed onto C57BL/6J for 10 generations before crossing to C57BL/6J-Hoxa13^Hd/+ at N7. This Hoxa13^Hd Mcoln3^Va-J stock was sibling bred for 2 generations and backcrossed once to C57BL/6J and then crossed to the B6C3Fe-a/a F1 hybrid and maintained by continued crosses to this hybrid. In 1987 B6C3F1-a/a F1 females were bred with Hoxa13^Hd Mcoln3^Va-J/+ + males at N5F2 to generate embryos for cryopreservation.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; ASP; SHEP9
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
Molecular note: Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039

Allele

Symbol: Mcoln3^Va-J
Name: varitint waddler Jackson
MGI accession ID: MGI:1856231
Generation method: Spontaneous
Synonyms: Va^J
Marker symbol: Mcoln3
Marker name: mucolipin 3
Marker synonyms: 6720490O21Rik; TRPML3; TRP-ML3; Va; varitint-waddler
Chromosome: 3
Strain of origin: STOCK Mcoln3^Va
Molecular note: This allele has a T-to-C transition at coding nucleotide 1085 within exon 8. This results in a change from isoleucine to threonine at amino acid 362 (p.I362T) in the second extracellular loop. The Mcoln3^Va-J allele, which arose on a strain segregating for the more severe Mcoln3^Va allele, also has the G-to-C transversion at coding nucleotide 1255 (p.A419P) specific to the Mcoln3^Va allele indicating that the Mcoln3^Va-J allele contains an additional point mutation to the Mcoln3^Va allele. The less severe phenotype of the Mcoln3^Va-J allele suggests that the T-to-C transition at nucleotide 1085 might mitigate the effects of the G-to-C mutation at nucleotide 1255 although the impact of genetic background must be considered. The encoded protein can be detected in the hair cells of heterozygous and homozygous mice.
General note: This mutation was found in a linkage cross involving Mcoln3^Va, and probably arose by mutation from Mcoln3^Va. (J:5286)

Allele

Symbol: Hoxa13^Hd
Name: hypodactyly
MGI accession ID: MGI:1857336
Generation method: Spontaneous
Synonyms: Hd
Marker symbol: Hoxa13
Marker name: homeobox A13
Marker synonyms: HOX1; Hox-1.10; HOX1J; RGD1562483
Chromosome: 6
Strain of origin: MYA/Hu
Molecular note: A 50-base pair deletion in the first exon of the Hd allele that probably arose from unequal recombination or misalignment between triplet repeats.
General note:

A double mutant of the hydrocephalic-polydactyly mutation, hop^hpy, and the hypodactyly mutation, Hoxa13^Hd, produced offspring of normal hallux phenotype. The first mutant tends to multiply, the second to eliminate halluces, and the two cancel each other (J:23839).