Overview

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 hyp...

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Mcoln3^Va-J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Mcoln3	mucolipin 3

Hoxa13^Hd

Allele Type	Gene Symbol	Gene Name
Spontaneous	Hoxa13	homeobox A13

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Research Applications

Developmental Biology Research
Dermatology Research
Neurobiology Research
Sensorineural Research

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$2,854.50 Domestic price Cryo Recovery

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Details

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.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Genetics

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039
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.

Mcoln3^Va-J

Allele Symbol: Mcoln3^Va-J

Allele Name	varitint waddler Jackson
Allele Type	Spontaneous
Allele Synonym(s)	Va^J
Gene Symbol and Name	Mcoln3, mucolipin 3
Gene Synonym(s)
Strain of Origin	STOCK Mcoln3^Va
Chromosome	3
General Note	This mutation was found in a linkage cross involving Mcoln3^Va, and probably arose by mutation from Mcoln3^Va. (J:5286)
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.

Hoxa13^Hd

Allele Symbol: Hoxa13^Hd

Allele Name	hypodactyly
Allele Type	Spontaneous
Allele Synonym(s)	Hd
Gene Symbol and Name	Hoxa13, homeobox A13
Gene Synonym(s)
Strain of Origin	MYA/Hu
Chromosome	6
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).
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.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

hand-foot-genital syndrome

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Hoxa13^Hd related

Developmental Biology Research
- Skeletal Defects
  - Oligodactyly

Genotype: Mcoln3^Va-J related

Dermatology Research
- Color and White Spotting Defects
Neurobiology Research
- Hearing Defects
- Vestibular Defects
Sensorineural Research
- Hearing Defects
- Vestibular Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mcoln3^Va-J/Mcoln3^Va-J
Not Specified

hearing/vestibular/ear phenotype

deafness

integument phenotype

variegated coat color
- mostly white with patches of dilute color

white spotting

diluted coat color

mammalian phenotype

behavior/neurological phenotype
- mice swim and behave normally
- Normal - able to swim
- Normal - both sexes are fertile and do not have the abnormal behavior of Mcoln3^Va

pigmentation phenotype

diluted coat color

variegated coat color
- mostly white with patches of dilute color

white spotting

Genotype: Mcoln3^Va-J/?
involves: A/J * C57BL/6J

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 12 weeks of age F2 progeny of a cross to A/J fail to respond to a 16 kHz stimulus at >100 dB, indicating that there are no background modifiers ameliorating this phenotype

Genotype: Mcoln3^Va-J/Mcoln3⁺
Not Specified

hearing/vestibular/ear phenotype

deafness

mammalian phenotype

behavior/neurological phenotype
- Normal - behave normally unlike Mcoln3^Va

pigmentation phenotype

variegated coat color
- a slightly dilute coat color, large irregular belly spots and white feet and tail tips
- not as varicolored as unlike Mcoln3^Va

belly spot
- mice exhibit a large, irregular belly spot

non-pigmented tail tip

abnormal foot pigmentation
- white feet

diluted coat color

integument phenotype

belly spot
- mice exhibit a large, irregular belly spot

diluted coat color

non-pigmented tail tip

variegated coat color
- a slightly dilute coat color, large irregular belly spots and white feet and tail tips
- not as varicolored as unlike Mcoln3^Va

abnormal foot pigmentation
- white feet

limbs/digits/tail phenotype

non-pigmented tail tip

Genotype: Mcoln3^Va-J/?
involves: C3HeB/FeJLe * C57BL/6J

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 12 weeks of age F2 progeny of a cross to C3HeB/FeJLe fail to respond to a 16 kHz stimulus at >100 dB, indicating that there are no background modifiers ameliorating this phenotype

Genotype: Mcoln3^Va-J/?
involves: BALB/cByJ * C57BL/6J

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 12 weeks of age F2 progeny of a cross to BALB/cByJ fail to respond to a 16 kHz stimulus at >100 dB, indicating that there are no background modifiers ameliorating this phenotype

Genotype: Mcoln3^Va-J/?
involves: C57BL/6J * CZECHII/EiJ

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 12 weeks of age F2 progeny of a cross to CZECHII/EiJ fail to respond to a 16 kHz stimulus at >100 dB, indicating that there are no background modifiers ameliorating this phenotype

Genotype: Mcoln3^Va-J/?
involves: C57BL/6J * DBA/2J

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 12 weeks of age F2 progeny of a cross to DBA/2J fail to respond to a 16 kHz stimulus at >100 dB, indicating that there are no background modifiers ameliorating this phenotype

Genotype: Mcoln3^Va-J/Mcoln3^Va-J
B6.Cg-Mcoln3

mortality/aging

prenatal lethality, incomplete penetrance
- Background Sensitivity - at backcross generation N6 to C57BL/6J intercrossing heterozygotes yields only 8% homozygous offspring

The following phenotype relates to a compound genotype created using this strain

Genotype: Hoxa13^Hd/Hoxa13⁺
B6C3Fe-a/a Hoxa13 Mcoln3/J

endocrine/exocrine gland phenotype

abnormal prostate gland anterior lobe morphology
- 29% have one lobe of the coagulating gland duct that has a single main duct

abnormal branching involved in seminal vesicle morphogenesis
- little secondary and tertiary branching is observed

decreased prostate gland duct number
- decrease in the number of duct tips in the dorsal and lateral divisions of the dorsolateral prostate and the ventral prostate

small prostate gland ventral lobe
- 43% have a smaller ventral prostate

abnormal seminal vesicle morphology
- seminal vesicles have an altered curvature and spiked clefting and lack the secondary and tertiary branches

abnormal ampullary gland morphology
- decrease in the number of duct tips in the ampullary gland

small seminal vesicle
- 86% have seminal vesicles that are two thirds the size of wild-type

small prostate gland
- 57% have a smaller dorsal prostate, 43% have a smaller lateral prostate, and 43% have a smaller ventral prostate

reproductive system phenotype

abnormal ampullary gland morphology
- decrease in the number of duct tips in the ampullary gland

abnormal uterine cervix morphology
- exhibit an anterior transformation of cervical tissue to a uterine stromal phenotype

decreased prostate gland duct number
- decrease in the number of duct tips in the dorsal and lateral divisions of the dorsolateral prostate and the ventral prostate

small prostate gland
- 57% have a smaller dorsal prostate, 43% have a smaller lateral prostate, and 43% have a smaller ventral prostate

small prostate gland ventral lobe
- 43% have a smaller ventral prostate

abnormal prostate gland anterior lobe morphology
- 29% have one lobe of the coagulating gland duct that has a single main duct

abnormal branching involved in seminal vesicle morphogenesis
- little secondary and tertiary branching is observed

abnormal seminal vesicle morphology
- seminal vesicles have an altered curvature and spiked clefting and lack the secondary and tertiary branches

small seminal vesicle
- 86% have seminal vesicles that are two thirds the size of wild-type

Genotype: Mcoln3^Va-J/Mcoln3⁺
B6C3Fe-a/a Hoxa13 Mcoln3/J

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 2 weeks of age heterozygotes respond to 8- and 16-kHz stimuli only at sound pressure levels of 88 dB and 94 dB respectively, no response was found to click or 32 kHz stimuli, and at 3 weeks of age thresholds increased to >100 dB, which, although it is an early and rapidly progressing hearing loss, is a less severe phenotype than in mice heterozygous for the original veritant waddler mutation
- an early and rapidly progressing hearing loss, is a less severe phenotype than in mice heterozygous for the original veritant waddler mutation

integument phenotype

belly spot
- heterozygotes express a small white ventral spot

diluted coat color
- heterozygotes express a slightly diluted coat color which is less diluted than that of the original veritant waddler heterozygotes

head spot
- some heterozygotes have a white forehead patch

pigmentation phenotype

diluted coat color
- heterozygotes express a slightly diluted coat color which is less diluted than that of the original veritant waddler heterozygotes

belly spot
- heterozygotes express a small white ventral spot

head spot
- some heterozygotes have a white forehead patch

Genotype: Hoxa13^Hd/Hoxa13^Hd
B6C3Fe-a/a Hoxa13 Mcoln3/J

reproductive system phenotype

abnormal uterine cervix morphology
- exhibit an anterior transformation of cervical tissue to a uterine stromal phenotype
- stromal tissue surrounding the cervical canals is smaller and the cervical canal is greatly reduced in size
- the columnar-to-squamosal epithelial transition that characterizes mature cervical-vaginal tissue is positioned within uterine-like stroma rather than cervical tissue

male infertility

short perineum
- 5 of 6 females exhibit a reduced ano-vaginal distance

abnormal penile bone morphology
- the proximal part of the penial bone is mishapen

dilated uterine horn
- 5 of 18 females exhibit enlarged, fluid-filled uterine horns

uterine cervix hypoplasia
- cervix is hypoplastic

female infertility

small penile bone
- the proximal part of the penial bone is smaller

small vagina
- profoundly small vaginal cavity

vesicovaginal fistula
- 1 of 18 females exhibit an abnormal fistula connecting the bladder and vaginal cavity

digestive/alimentary phenotype

short perineum
- 5 of 6 females exhibit a reduced ano-vaginal distance

intestinal obstruction
- 2 of 3 males exhibit bowel obstructions

renal/urinary system phenotype

absent urinary bladder
- 1 of 18 females lack a bladder

urinary bladder cysts
- 2 of 3 males exhibit cystic bladders

vesicovaginal fistula
- 1 of 18 females exhibit an abnormal fistula connecting the bladder and vaginal cavity

kidney cysts
- 3 of 18 females exhibit cystic kidneys

abnormal renal/urinary system morphology
- one third of females exhibit urinary tract defects

small penile bone
- the proximal part of the penial bone is smaller

urinary bladder hypoplasia
- 1 of 3 males exhibit a hypoplastic bladder

renal hypoplasia
- 1 of 18 females exhibt a hypoplastic kidney

abnormal female urethra morphology
- urethra is abnormally located within the serosal layer in females

abnormal penile bone morphology
- the proximal part of the penial bone is mishapen

Genotype: Mcoln3^Va-J/Mcoln3^Va-J
B6C3Fe-a/a Hoxa13 Mcoln3/J

integument phenotype

mottled coat
- homozygotes are almost entirely variegated both ventrally and dorsally

pigmentation phenotype

mottled coat
- homozygotes are almost entirely variegated both ventrally and dorsally

References

Additional References

Di Palma F; Belyantseva IA; Kim HJ; Vogt TF; Kachar B; Noben-Trauth K. 2002. Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. Proc Natl Acad Sci U S A 99(23):14994-9PubMed: 12403827 MGI: J:80336
Kim HJ; Jackson T; Noben-Trauth K. 2003. Genetic analyses of the mouse deafness mutations varitint-waddler (va) and jerker (espnje). J Assoc Res Otolaryngol 4(1):83-90PubMed: 12209292 MGI: J:78812
Lane PW. 1972. Two new mutations in linkage group XVI of the house mouse. Flaky tail and varitint-waddler-J. J Hered 63(3):135-40PubMed: 4557539 MGI: J:5286

Additional - a related

Additional - Hoxa13^Hd related

Additional - Mcoln3^Va-J related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

Mcoln^Va-J and Hoxa13^Hd are on separate chromosomes and assort independently. The mice distributed are heterozygous carriers for either one or the other mutation, but not both.
- Additional Breeding and Husbandry Support
Appearance
- Hoxa13^Hd: black, toe defects to hindfeet
  Related Genotype: a/a Hoxa13^Hd/+ +/+
  
  Mcoln3^Va-J: slightly diluted black with spotting on belly or head, ataxic
  Related Genotype: Mcoln3^Va-J/+ +/+
  
  Mcoln3^Va-J: agouti, unaffected
  Related Genotype: A/A +/+ +/+
  
  Hoxa13^Hd: black unaffected
  Related Genotype: a/a +/+ +/+
Citation
When using the B6C3Fe-a/a Hoxa13^Hd Mcoln3^Va-J/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000296 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for a,Heterozygous or Wild-type for Mcoln3<Va-J>,Heterozygous or Wild-type for Hoxa13<Hd>

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

a

Allele Symbol: a

Mcoln3Va-J

Allele Symbol: Mcoln3Va-J

Hoxa13Hd

Allele Symbol: Hoxa13Hd

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Hoxa13Hd related

Genotype: Mcoln3Va-J related

Mammalian Phenotype Terms by Genotype

Genotype: Mcoln3Va-J/Mcoln3Va-JNot Specified

hearing/vestibular/ear phenotype

integument phenotype

mammalian phenotype

pigmentation phenotype

Genotype: Mcoln3Va-J/?involves: A/J * C57BL/6J

hearing/vestibular/ear phenotype

Genotype: Mcoln3Va-J/Mcoln3+Not Specified

hearing/vestibular/ear phenotype

mammalian phenotype

pigmentation phenotype

integument phenotype

limbs/digits/tail phenotype

Genotype: Mcoln3Va-J/?involves: C3HeB/FeJLe * C57BL/6J

hearing/vestibular/ear phenotype

Genotype: Mcoln3Va-J/?involves: BALB/cByJ * C57BL/6J

hearing/vestibular/ear phenotype

Genotype: Mcoln3Va-J/?involves: C57BL/6J * CZECHII/EiJ

hearing/vestibular/ear phenotype

Genotype: Mcoln3Va-J/?involves: C57BL/6J * DBA/2J

hearing/vestibular/ear phenotype

Genotype: Mcoln3Va-J/Mcoln3Va-JB6.Cg-Mcoln3

mortality/aging

Genotype: Hoxa13Hd/Hoxa13+B6C3Fe-a/a Hoxa13 Mcoln3/J

endocrine/exocrine gland phenotype

reproductive system phenotype

Genotype: Mcoln3Va-J/Mcoln3+B6C3Fe-a/a Hoxa13 Mcoln3/J

hearing/vestibular/ear phenotype

integument phenotype

pigmentation phenotype

Genotype: Hoxa13Hd/Hoxa13HdB6C3Fe-a/a Hoxa13 Mcoln3/J

reproductive system phenotype

digestive/alimentary phenotype

renal/urinary system phenotype

Genotype: Mcoln3Va-J/Mcoln3Va-JB6C3Fe-a/a Hoxa13 Mcoln3/J

integument phenotype

pigmentation phenotype

References

Additional References

Additional - a related

Additional - Hoxa13Hd related

Additional - Mcoln3Va-J related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Mcoln3^Va-J

Allele Symbol: Mcoln3^Va-J

Hoxa13^Hd

Allele Symbol: Hoxa13^Hd

Genotype: Hoxa13^Hd related

Genotype: Mcoln3^Va-J related

Genotype: Mcoln3^Va-J/Mcoln3^Va-J
Not Specified

Genotype: Mcoln3^Va-J/?
involves: A/J * C57BL/6J

Genotype: Mcoln3^Va-J/Mcoln3⁺
Not Specified

Genotype: Mcoln3^Va-J/?
involves: C3HeB/FeJLe * C57BL/6J

Genotype: Mcoln3^Va-J/?
involves: BALB/cByJ * C57BL/6J

Genotype: Mcoln3^Va-J/?
involves: C57BL/6J * CZECHII/EiJ

Genotype: Mcoln3^Va-J/?
involves: C57BL/6J * DBA/2J

Genotype: Mcoln3^Va-J/Mcoln3^Va-J
B6.Cg-Mcoln3

Genotype: Hoxa13^Hd/Hoxa13⁺
B6C3Fe-a/a Hoxa13 Mcoln3/J

Genotype: Mcoln3^Va-J/Mcoln3⁺
B6C3Fe-a/a Hoxa13 Mcoln3/J

Genotype: Hoxa13^Hd/Hoxa13^Hd
B6C3Fe-a/a Hoxa13 Mcoln3/J

Genotype: Mcoln3^Va-J/Mcoln3^Va-J
B6C3Fe-a/a Hoxa13 Mcoln3/J

Additional - Hoxa13^Hd related

Additional - Mcoln3^Va-J related