Overview

This inbred mutant strain carries the wabbler-lethal (Atp8a2^wl) and hairless (Hr^hr) spontaneous mutations that are maintained in repulsion.

Genetic overview

Genetic Background	Generation

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Research Applications

Metabolism Research
Neurobiology Research
Sensorineural Research
Cancer Research
Research Tools
Dermatology Research
Immunology, Inflammation and Autoimmunity Research
Cardiovascular Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Important Note

This strain is homozygous for Esd^c and segregating for Hr^hr and wl, which are held in repulsion.

Detailed Description

WLHR/Le is a balanced stock with wabbler-lethal (wl) and hairless (hr) spontaneous mutations maintained in repulsion on Chromosome 14. Homozygous wabbler-lethal mutant mice are first recognizable at 12 days of age and usually die at about four weeks. They have an abnormal wobbly gait and a pronounced tremor when walking. In an extensive study of behavioral development of this mutant, homozygous wabbler-lethal mice were shown to be deficient in nearly all behaviors tested. Histological examination showed myelin degeneration widely distributed throughout the CNS, particularly in the vestibulocerebellar and spinocerebellar systems. Electron microscopy showed widespread axonal (Wallerian) degeneration in the medulla with secondary myelin dissolution. Similar abnormalities were present to a lesser extent in the basal ganglia, spinal cord, and cerebellum and in the optic nerve. Homozygous hairless mutant mice have a higher incidence and earlier onset of leukemia, reducible by virus-specific antibody. A deficiency of splenic T helper cells (Ly1⁺) may account for low cellular immune response of homozygous mutant mice. The coat is normal on hairless mice up to 10 days but then hair is lost from the follicle. Waves of hair growth with few thin fuzzy hairs ocur at monthly intervals for some time but homozygotes eventually become continuously hairless. Vibrissae are repeatedly regrown and shed, becoming more abnormal with age. Toenails are long and curved. There is hyperkeratosis of statified epithelium and the upper part of hair canals beginning at 14 days. Hair club formation is abnormal. Cysts form from the hyperkeratotic upper part of hair canals and sheaths of abnormal follicles stranded in dermis. Some cysts also form from sebaceous glands. All cysts undergo sebaceous transformation and later keratinization.

Development

The first wabbler lethal (wl) mouse appeared in descendents of a non-inbred pirouette (pi/pi) mouse carrying brown (Typr1^b) and nonagouti (a) that was returned to the Jackson Laboratory from Dr. R. A. Fisher in 1948 after the fire. The pirouette male was mated to a C57BL/6J female and several lines were made. An outcross was also made to strain HD/Hu of Dr. Katrina Hummel. Strain HD/Hu was homozygous for hairless (Hr^hr) and dilute (Myo5a^d). The stock was bred using tested but non-sibling matings until 1958 when inbreeding was started as a balanced stock with wl and hr in repulsion phase because they were closely linked on chromosome 14. The stock was also selected to be homozygous brown and nonagouti. It was cryopreserved in 1989 by mating known doubly heterozygous males to either known heterozygous or untested females at generations F115-120.

Genetics

Atp8a2^wl

Allele Symbol: Atp8a2^wl

Allele Name	wabbler lethal
Allele Type	Spontaneous
Allele Synonym(s)	Wl
Gene Symbol and Name	Atp8a2, ATPase, aminophospholipid transporter-like, class I, type 8A, member 2
Gene Synonym(s)
Strain of Origin	STOCK Grxcr1^pi
Chromosome	14
Molecular Note	Spontaneous deletion of 21 bp in exon 22 results in elimination of seven highly conserved amino acids (AIEDRLQ or IEDRLQA) from the nucleotide-binding domain (N-domain).

Hr^hr

Allele Symbol: Hr^hr

Allele Name	hairless
Allele Type	Spontaneous
Allele Synonym(s)	hr; SKH-1
Gene Symbol and Name	Hr, lysine demethylase and nuclear receptor corepressor
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	14
Molecular Note	The hr allele is the result of a retroviral integration. Insertion of murine leukemia proviral sequences into intron 6 results in aberrant splicing of the gene.

Esd

Marker Symbol: Esd

Marker Synonym(s)
Chromosome(s)	14

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).

cerebellar ataxia, mental retardation and dysequlibrium syndrome

Research Areas By Phenotype

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

Metabolism Research

Genotype: Atp8a2^wl related

Neurobiology Research
- Ataxia (Movement) Defects
- Myelination Defects
- Tremor Defects
- Vestibular Defects
Sensorineural Research
- Vestibular Defects

Genotype: Hr^hr related

Cancer Research
- Increased Tumor Incidence
  - Skin Cancers: Induced
  - Leukemia
  - Lymphomas
  - Skin Cancers
  - Leukemia: lymphocytic
  - Lymphomas: thymic
- Toxicology
Research Tools
- Toxicology Research
  - drug/compound testing
Dermatology Research
- Skin and Hair Texture Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
Cardiovascular Research
- Diet-Induced Atherosclerosis
  - Relatively Resistant

Mammalian Phenotype Terms by Genotype

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

Genotype: Hr^hr/Hr^hr
Not Specified

behavior/neurological phenotype

abnormal nursing
- failure

endocrine/exocrine gland phenotype

abnormal mammary gland morphology
- nipple at bottom of cup-shaped depression in skin
- no ducts
- small

sebaceous gland atrophy

integument phenotype

abnormal dermis reticular layer morphology
- cystic

abnormal mammary gland morphology
- nipple at bottom of cup-shaped depression in skin
- no ducts
- small

abnormal skin morphology
- thickened cutis

deformed nails
- curved

dermal cysts

epidermal hyperplasia

hairless
- beginning ~15 days of age and progressing from nose back

hyperkeratosis

sebaceous gland atrophy

Genotype: Hr^hr/Hr^hr
HRS/J

cellular phenotype

decreased T cell proliferation
- to alloantigens by T helper cells

hearing/vestibular/ear phenotype

absent linear vestibular evoked potential
- VESPs are absent at the maximum stimulus intensity used

hematopoietic system phenotype

decreased T cell number
- of CD5+ T cells

decreased T cell proliferation
- to alloantigens by T helper cells

increased macrophage cell number
- although heterozygotes and homozygotes have the same total number of peritoneal cells, the percentage expressing Mac-1 is an average of 30% in homozygotes versus an average of 14% in heterozygotes

immune system phenotype

decreased T cell number
- of CD5+ T cells

decreased T cell proliferation
- to alloantigens by T helper cells

increased macrophage cell number
- although heterozygotes and homozygotes have the same total number of peritoneal cells, the percentage expressing Mac-1 is an average of 30% in homozygotes versus an average of 14% in heterozygotes

neoplasm

increased leukemia incidence
- at 8 to 10 months of age 45% of homozygotes have lymphoid leukemia, compared with only 1% in heterozygotes, and approximately 72% of these homozygotes develop myeloid leukemia later in life up to 18 months of age
- increased incidence

Genotype: Atp8a2^wl/Atp8a2^wl
Not Specified

behavior/neurological phenotype

abnormal gait

abnormal motor coordination/balance
- swaying of the body, dragging of the hind limbs and progressive incoordination of the limbs when walking

abnormal reflex
- no reaction to pinching of the tail

ataxia
- homozygotes have difficulty in walking and when trying to walk seem to pull the hind feet along rather than pushing off with them

impaired limb coordination

limb grasping
- when homozyogtes are lifted by the tail, the hind feet lock together in a spasm

tremors

mammalian phenotype

behavior/neurological phenotype
- Normal - can orient in water and swim

hearing/vestibular/ear phenotype
- Normal - normal hearing and auditory reflexes

nervous system phenotype
- Normal - demyelination is not found in the telencephalon at 2.5 weeks of age
- Normal - there is no myelin degeneration detected in the thalamus

mortality/aging

lethality at weaning, complete penetrance
- most homozygotes die by wean age, with males dying at approximately 3 weeks of age and females dying approximately a week later

nervous system phenotype

demyelination
- at one week of age a small amount of myelin degeneration can be found in the ventral funiculus of the spinal cord; at two weeks of age myelin degeneration is marked in the vestibulo-spinal tracts and beginning in the spino-cerebellar tracts; and by 2.5 weeks of age very severe demyelination is found throughout the archi- and paleocerebellar systems, with heavy degeneration permeating the vestibulo-spinal tract, dorsal spinocerebellar tract, brachium conjunctivum, magnocellular red nucleus, rubrospinal tract, vestibular nerve and nuclei, juxtarestiform body, trapezoid body and the superior olivary nucleus, and moderate degeneration in the medial lemnicus, medial longitudinal fasiculus and tecto-spinal tracts
- body, the lateral lemniscus, brachium conjunctivum, red nucleus, and the rubrospinal and tectospinal tracts
- ct, vestibular nerve and nuclei, juxtarestiform body, trapezoid body and the superior olivary nucleus, and moderate degeneration in the medial lemnicus, medial longitudinal fasiculus and tecto-spinal tracts
- eks of age very severe demyelination is found throughout the archi- and paleocerebellar systems, with heavy degeneration permeating the vestibulo-spinal tract, dorsal spinocerebellar tract, brachium conjunctivum, magnocellular red nucleus, rubrospinal tra
- in the vestibulosponal tract from the lateral vestibular nucleus to the spinal cord, and in the entering fibers of the eighth cranial nerve, the juxtaresiform body, the medullary center of the cerebellum, the medial longitudinal fasciculus, the trapezoid body, the lateral lemniscus, brachium conjunctivum, red nucleus, and the rubrospinal and tectospinal tracts

homeostasis/metabolism phenotype

abnormal circulating amino acid level
- plasma phenylalanine concentration rises after 18 days of age to abnormally high levels and phenylalanine loading experiments show that at 22 days of age homozygotes can not normally metabolize exogenous phenylalanine, although they can at 14 days of age

abnormal enzyme/coenzyme level
- activity, increased tryptophan-alpha-ketoglutarate activity, and increased tryptophan pyrrolase activity
- liver homogenates have decreased phenylalanine hydroxylase activity, decreased phenylalanine-sodium pyruvate transaminase activity, and increased phenylalanine-alpha-ketoglutarate transaminase activity, increased tyrosine-alpha-ketoglutarate transaminase activity, increased tryptophan-alpha-ketoglutarate activity, and increased tryptophan pyrrolase activity

hypoglycemia
- mice are hypoglycemic from 20 days until death

increased circulating tyrosine level
- me progressively lower to 26 days of age (14.13 ug/ml vs 22.18 ug/ml in heterozygotes), although loading experiments show that homozygotes handle added tyrosine and tryptophan in a manner comparable to that of heterozygous littermates
- plasma tyrosine concentration is higher than normal at 14 days of age then rapidly drops to abnormally low levels (at 26 days of age 13.36 ug/ml vs 23.12 ug/ml in heterozygotes) and plasma tryptophan levels are lower than normal at 14 days of age and become progressively lower to 26 days of age (14.13 ug/ml vs 22.18 ug/ml in heterozygotes), although loading experiments show that homozygotes handle added tyrosine and tryptophan in a manner comparable to that of heterozygous littermates

Genotype: Atp8a2^wl/Atp8a2⁺
Not Specified

behavior/neurological phenotype

abnormal motor coordination/balance
- all heterozygotes are not symptomatic
- symptoms are subtle and obvious only to experienced observers

ataxia
- Background Sensitivity - heterozygous mice are distinguishable from normal mice only in exceptional cases
- mild ataxia is characterized by the hind feet going out to the side more than normal and the body being closer to the ground

nervous system phenotype

demyelination
- at 2 weeks of age a small amount of myelin degeneration is found in the vestibulo-spinal tract and at 2.5 weeks myelin degeneration is still confined to the vestibulo-spinal pathway with the cerebellar systems unaffected
- moderate demyelination restricted to the vestibulospinal tract

Genotype: Atp8a2^wl/Atp8a2^wl
involves: C57BL/6J

growth/size/body region phenotype

decreased body weight
- at 28 days of age the average weight of males, 6.3g, is less than half that of normal controls, 14.2g

nervous system phenotype

optic nerve degeneration
- at 28 days of age there is primary axonal degeneration of the optic nerve, but significant dysmyelination or hypomyelination are not found in the optic nerves at this timepoint

vision/eye phenotype

optic nerve degeneration
- at 28 days of age there is primary axonal degeneration of the optic nerve, but significant dysmyelination or hypomyelination are not found in the optic nerves at this timepoint

Genotype: Atp8a2^wl/Atp8a2^wl
involves: C57BL/6

behavior/neurological phenotype

decreased startle reflex

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 2 months

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - outer and inner hair cells appear normal

vision/eye phenotype
- Normal - outer segment photoreceptors exhibit normal morphology

nervous system phenotype

cochlear ganglion degeneration
- at 2 months

decreased retinal photoreceptor cell number
- at P30 and P60

short photoreceptor outer segment
- at P30 and P60

vision/eye phenotype

decreased retinal photoreceptor cell number
- at P30 and P60

short photoreceptor outer segment
- at P30 and P60

References

Additional References

Cachon-Gonzalez MB; Fenner S; Coffin JM; Moran C; Best S; Stoye JP. 1994. Structure and expression of the hairless gene of mice. Proc Natl Acad Sci U S A 91(16):7717-21PubMed: 8052649 MGI: J:19624
Morrissey PJ; Parkinson DR; Schwartz RS; Waksal SD. 1980. Immunologic abnormalities in HRS/J mice. I. Specific deficit in T lymphocyte helper function in a mutant mouse. J Immunol 125(4):1558-62PubMed: 6447727 MGI: J:6375
Reske-Kunz AB; Scheid MP; Boyse EA. 1979. Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice. J Exp Med 149(1):228-33PubMed: 310859 MGI: J:6087

Additional - Atp8a2^wl related

Additional - Esd related

Additional - Hr^hr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Hr
- Genotyping resources and troubleshooting
Mating System
- Progeny Tested
- TJL Breeding Scheme: progeny test
- for hr: heterozygote x heterozygote in repulsion with wl
- for wl: heterozygote x heterozygote in repulsion with hr
- for Es10^c: homozygote x homozygote
  TJL Breeding Summary: hr + Es10^c/+ wl Es10^c X hr + Es10^c/+ wl Es10^c. This yields progeny of three genotypes that can be identified phenotypically before weaning
- see Strain Description above
Appearance
- brown, haired, normal gait
  Related Genotype: a/a Tyrp1^b/Tyrp1^b wl + Esd^c/+ Hr^hr Esd^c or a/a Tyrp1^b/Tyrp1^b ? + Esd^c/+ ? Esd^c
  
  brown, haired, wobbly gait
  Related Genotype: a/a Tyrp1^b/Tyrp1^b + wl Esd^c/? wl Esd^c
  
  pigmented, hairless, normal gait
  Related Genotype: a/a Tyrp1^b/Tyrp1^b Hr^hr + Esd^c/Hr^hr ? Esd^c
Citation
When using the WLHR/LeJ mouse strain in a publication, please include JAX stock #000147 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,Homozygous for Tyrp1<b>, Homozygous for Esdc, Genes in Repulsion: Assumed Heterozygous for wl(Untested),Heterozygous for hr

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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.

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Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Atp8a2wl

Allele Symbol: Atp8a2wl

Hrhr

Allele Symbol: Hrhr

Esd

Marker Symbol: Esd

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: Atp8a2wl related

Genotype: Hrhr related

Mammalian Phenotype Terms by Genotype

Genotype: Hrhr/HrhrNot Specified

behavior/neurological phenotype

endocrine/exocrine gland phenotype

integument phenotype

Genotype: Hrhr/HrhrHRS/J

cellular phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

immune system phenotype

neoplasm

Genotype: Atp8a2wl/Atp8a2wlNot Specified

behavior/neurological phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

homeostasis/metabolism phenotype

Genotype: Atp8a2wl/Atp8a2+Not Specified

behavior/neurological phenotype

nervous system phenotype

Genotype: Atp8a2wl/Atp8a2wlinvolves: C57BL/6J

growth/size/body region phenotype

nervous system phenotype

vision/eye phenotype

Genotype: Atp8a2wl/Atp8a2wlinvolves: C57BL/6

behavior/neurological phenotype

hearing/vestibular/ear phenotype

mammalian phenotype

nervous system phenotype

vision/eye phenotype

References

Additional References

Additional - Atp8a2wl related

Additional - Esd related

Additional - Hrhr related

Genotyping Protocols

Mating System

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Atp8a2^wl

Allele Symbol: Atp8a2^wl

Hr^hr

Allele Symbol: Hr^hr

Genotype: Atp8a2^wl related

Genotype: Hr^hr related

Genotype: Hr^hr/Hr^hr
Not Specified

Genotype: Hr^hr/Hr^hr
HRS/J

Genotype: Atp8a2^wl/Atp8a2^wl
Not Specified

Genotype: Atp8a2^wl/Atp8a2⁺
Not Specified

Genotype: Atp8a2^wl/Atp8a2^wl
involves: C57BL/6J

Genotype: Atp8a2^wl/Atp8a2^wl
involves: C57BL/6

Additional - Atp8a2^wl related

Additional - Hr^hr related