Overview

This C57BL/10Sn congenic strain carries two closely linked Chromosome 2 alleles, pallid (Bloc1s6^pa) and the minor histocompatibility 3^e allele along with the Chromosome 2 black and tan allele (a^t).

Genetic overview

Genetic Background	Generation

Bloc1s6^pa

Allele Type	Gene Symbol	Gene Name
Spontaneous	Bloc1s6	biogenesis of lysosomal organelles complex-1, subunit 6, pallidin

a^t

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Marker(s)

	Marker Symbol	Marker Name
	H3	histocompatibility 3

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Dermatology Research
Hematological Research
Internal/Organ Research
Neurobiology Research
Sensorineural Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

This minor histocompatibility 3 (H3^e) congenic strain is also carrying the closely linked pallid mutation (Bloc1s6^pa) as well as the black and tan allele of nonagouti also residing on Chromosome 2. Histocompatibility 3 is one of several loci isolated and identified by Dr. George Snell and co-workers. Histocompatibility gene differences were identified by generating congenic resistant strains and testing for resistance to transplantable tumors. Homozygous pallid mice have pink eyes, a diluted coat color and their viability is slightly reduced. Some homozygotes have slightly abnormal behavior, with abnormal postural responses and head tilting due to the absence of otoliths in the sacculus and utriculus in many but not all mutant mice. The effect of pallid on behavior and otolith morphology appears to be a result of manganese deficiency. Homozygotes display defective mucopolysaccharide synthesis in the otolith matrix and a slower rate of transport of manganese, L-dopa, and L-tryptophane in the brain. Homozygotes have elevated basal and testosterone-induced levels of the kidney lysosomal enzymes b-glucuronidase, b-galactosidase, and a-mannosidase, accompanied by lowered enzyme excretion in the urine. Pallid mice have a deficiency in serum a1-antitrypsin and have been proposed as a model of genetic a1-antitrypsin deficiency. Lung lesions similar to those seen in human emphysema are found in these mice, and are attributed, like human hereditary emphysema, to a decreased capacity to inhibit serum elastase although liver a1-antitrypsin activity is normal. Pallid mice have prolonged bleeding time due to a platelet storage pool deficiency (SPD) characterized by a normal platelet number but a deficiency in the number of platelet dense granules and in the serotonin, ATP, and ADP content of the granules. Two other mouse coat color mutants, muted (Bloc1s5^mu) and mocha (Ap3d1^mh), present a similar concatenation of pigment, otolith, and platelet SPD abnormalities, which also occur in human Hermansky-Pudlak syndrome.

Development

This strain was developed by G. Snell and he referred to it as B10.PA-H3^e. It was previously called B10-pa H-3^e a^t and was derived by repeated backcrossing of pa H-3^e We Un from B6-pa/Re to strain B10.UW (Stock No. 000419). The allele a^t in B10.PA-Bloc1s6^pa H3^e a^t/SnJ was derived from B10.UW. B10.PA-Bloc1s6^pa H3^e a^t/SnJ embryos were cryopreserved in 1996 at generation N11F76.

Control Suggestions

000666 C57BL/10SnJ

Additional Information

Considerations for Choosing Controls

Genetics

Bloc1s6^pa

Allele Symbol: Bloc1s6^pa

Allele Name	pallid
Allele Type	Spontaneous
Allele Synonym(s)	pa; Pldn^suppa^/sup; Pldnpa
Gene Symbol and Name	Bloc1s6, biogenesis of lysosomal organelles complex-1, subunit 6, pallidin
Gene Synonym(s)
Strain of Origin	wild
Chromosome	2
Molecular Note	The C to T substitution at coding nucleotide 205 introduces a premature stop codon at arginine codon 69 (p.R69*) in pallid mice. Through Northern analysis, a single mRNA of about 2.5kb was found in reduced levels compared to wild-type.

a^t

Allele Symbol: a^t

Allele Name	black and tan
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	English fancy stock
Chromosome	2
General Note	This allele is recessive to A and A^w on the dorsum and dominant to all agouti alleles on the ventrum except for A^w from which it is indistinguishable (J:78801) .
Molecular Note	This allele comprises a 6 kb insertion containing a retrovirus-like transposable element VL30 and a single 526 bp repeat into the first intron of the agouti gene at the same position as for alleles a and A^w.

H3

Marker Symbol: H3

Marker Synonym(s)
Chromosome(s)	2

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).

Hermansky-Pudlak syndrome 9

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genotype: a^t related

Dermatology Research
- Color and White Spotting Defects

Genotype: Bloc1s6^pa related

Dermatology Research
- Color and White Spotting Defects
Hematological Research
- Platelet Defects
  - platelet storage pool deficiency
Internal/Organ Research
- Kidney Defects
  - lysosomal enzyme abnormalities
- Lung Defects
  - emphysema
Neurobiology Research
- Vestibular Defects
Sensorineural Research
- 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: Bloc1s6^pa/Bloc1s6^pa
involves: wild-derived

integument phenotype

diluted coat color
- pale agouti

pigmentation phenotype

decreased eye pigmentation
- pink eyes

diluted coat color
- pale agouti

vision/eye phenotype

decreased eye pigmentation
- pink eyes

Genotype: Bloc1s6^pa/Bloc1s6^pa
B6.Cg-Bloc1s6/J

behavior/neurological phenotype

ataxia
- exaggerated ataxia in some mice after a swim test

head tilt
- seen in about 25% of homozygotes

impaired balance
- sometimes seen to roll over at the end of a swim test

impaired swimming
- 55/99 mice unable to swim - related to absence of normal otoliths
- erratic swimming pattern in some mice with head tilt

tonic seizures
- momentary, in mice displaying head tilt when first placed in water for a swim test

hearing/vestibular/ear phenotype

abnormal linear vestibular evoked potential
- mice with absent otoconia show absent vestibular compound action potentials
- variable defects in latencies, amplitudes and thresholds of VESPs, dependent on amounts of otoconia present

abnormal otolith morphology
- otolith development improves by maternal feeding with increased levels of manganese during early gestation
- variable presence of otoliths - from normal to complete absence

hematopoietic system phenotype

abnormal NK cell physiology
- lower natural killer cell activity

abnormal platelet activation
- agonist-dependent lysosome release in platelets is impaired
- lysosomal enzyme secretion after thrombin activation about half normal
- platelets show impaired alpha granule content release in response to low-dose thrombin stimulation
- reduced serotonin release after thrombin activation
- stimulation with a low dose of thrombin elicits a muted release of lysosomal enzymes from platelets

abnormal platelet physiology

decreased platelet ADP level
- platelet ADP levels are a third to a half that of C57BL/6J controls

decreased platelet aggregation
- mice exhibit abnormal thrombus formation during laser-induced blood vessel damage, with total platelet accumulation severely attenuated by nearly 80%

decreased platelet ATP level
- platelet ATP levels are about half that of C57BL/6J controls

decreased platelet dense granule number
- fewer dense granules per platelet

decreased platelet serotonin level
- platetelet serotonin levels less than 1% of normal

homeostasis/metabolism phenotype

abnormal blood homeostasis
- serum elastase inhibitory capacity and alpha1-antitrypsin levels are significantly reduced compared to controls

abnormal platelet activation
- agonist-dependent lysosome release in platelets is impaired
- lysosomal enzyme secretion after thrombin activation about half normal
- platelets show impaired alpha granule content release in response to low-dose thrombin stimulation
- reduced serotonin release after thrombin activation
- stimulation with a low dose of thrombin elicits a muted release of lysosomal enzymes from platelets

abnormal platelet physiology

abnormal urine enzyme level
- reduced secretion of lysosomal enzymes into the urine of testosterone treated mice

decreased platelet aggregation
- mice exhibit abnormal thrombus formation during laser-induced blood vessel damage, with total platelet accumulation severely attenuated by nearly 80%

decreased platelet serotonin level
- platetelet serotonin levels less than 1% of normal

increased bleeding time
- greater than 15 minutes

pulmonary edema
- at 12 months of age edema is seen in patches of the interstitium

immune system phenotype

abnormal NK cell physiology
- lower natural killer cell activity

lung inflammation
- at 24 months of age lungs that don't display air space enlargement have scattered intraalveolar infiltration of inflammatory cells

integument phenotype

diluted coat color
- display a generalized pigmented dilution

mammalian phenotype

integument phenotype
- Normal - electron microscopy of the skin shows regular collagen bundles and no excess collagen deposition

mortality/aging

premature death
- survival beyond 16 months of age reduced to about 40%

nervous system phenotype

decreased platelet serotonin level
- platetelet serotonin levels less than 1% of normal

tonic seizures
- momentary, in mice displaying head tilt when first placed in water for a swim test

pigmentation phenotype

abnormal melanosome morphology
- do not increase in size with maturation
- immature melanosomes found in follicular melanocytes
- increased numbers of multivesicular forms
- striated forms more frequent as well but are usually misshapen and with irregular pigment

diluted coat color
- display a generalized pigmented dilution

ocular albinism
- near total iris albinism

renal/urinary system phenotype

abnormal kidney physiology
- increased rate of lysosomal enzyme synthesis in kidneys
- kidney beta-glucuronidase levels increased 2.5X
- kidney levels of beta-galactosidase and alpha-mannosidase increased

abnormal urine enzyme level
- reduced secretion of lysosomal enzymes into the urine of testosterone treated mice

respiratory system phenotype

abnormal lung interstitium morphology
- at 12 months of age large lipid droplets and edema are seen in patches of the interstitium
- at 8 months of age the interstitial matrix appears disorganized due to the presence of cytoplasmic remnants in the alveolar interstitium

abnormal lung morphology
- "honeycomb" effect on lung architecture
- at 8 months of age loss of endothelial cells accompanied by the presence of cellular debris in the alveolar spaces is seen
- by 12 months of age changes in lung morphology become more severe
- Normal - prior to 8 months of age no abnormalities are detected in the lung

abnormal lung volume
- lung volume is decreased at 8 months of age but increased at 12 and 28 months of age relative to age matched controls

abnormal pulmonary alveolus epithelium morphology
- at 8 months of age loss of epithelial cells accompanied by the presence of cellular debris in the alveolar spaces is seen

abnormal pulmonary alveolus morphology
- at 12 and 24 months of age some lungs show a few patchy areas of air space enlargement accompanied by alveolar septal destruction
- by 16 months of age, enlarged airspaces and destruction of alveolar tissue
- cellular debris in the alveolar spaces is seen in mice at 8 months of age

abnormal respiratory mechanics
- lung reactance values decrease with age relative to controls

abnormal respiratory system physiology
- lung elastin levels are significantly reduced compared to controls

emphysema
- emphysematous lesions are seen beginning at 12 months of age

lung inflammation
- at 24 months of age lungs that don't display air space enlargement have scattered intraalveolar infiltration of inflammatory cells

pulmonary edema
- at 12 months of age edema is seen in patches of the interstitium

vision/eye phenotype

ocular albinism
- near total iris albinism

cellular phenotype

abnormal lysosome physiology
- significant increase in lysosomal enzyme activity of beta-galactosidase and beta-glucuronidase, and to a lesser extent N-acetyl-beta-hexoseaminidase, in kidney extracts

growth/size/body region phenotype

increased body weight
- at 12 months of age but not at 8 or 28 months of age

Genotype: Bloc1s6^pa/Bloc1s6^pa
Not Specified

cellular phenotype

maternal effect
- homozygotes from dams fed a diet high in manganese during pregnancy do not display ataxia or the inability to orient in water

mammalian phenotype

cellular phenotype
- Normal - no apparent changes of intracellular Notch1 (N^TM) levels are observed in isolated mouse embryonic fibroblasts (MEFs) relative to wild-type MEFs

Genotype: a/a Bloc1s6^pa/Bloc1s6^pa
involves: C57BL/6J

pigmentation phenotype

abnormal retinal melanin granule morphology
- number of granules in the retina is greatly reduced
- size of granules is diminished

vision/eye phenotype

abnormal retinal melanin granule morphology
- number of granules in the retina is greatly reduced
- size of granules is diminished

References

Additional References

Gwynn B; Korsgren C; Cohen CM; Ciciotte SL; Peters LL. 1997. The gene encoding protein 4.2 is distinct from the mouse platelet storage pool deficiency mutation pallid. Genomics 42(3):532-5PubMed: 9205130 MGI: J:38773
Jones SM; Erway LC; Johnson KR; Yu H; Jones TA. 2004. Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191(1-2):34-40PubMed: 15109702 MGI: J:89392
White RA; Peters LL; Adkison LR; Korsgren C; Cohen CM; Lux SE. 1992. The murine pallid mutation is a platelet storage pool disease associated with the protein 4.2 (pallidin) gene. Nat Genet 2(1):80-3PubMed: 1284644 MGI: J:2185

Additional - a^t related

Additional - Bloc1s6^pa related

Additional - H3 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the B10.PA-Bloc1s6^pa H3^e a^t/SnJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #000477 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 Pldn<pa>, Homozygous for H3<e>, Homozygous for a<t>, 1 pair minimum

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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

Marker(s)

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Bloc1s6pa

Allele Symbol: Bloc1s6pa

at

Allele Symbol: at

H3

Marker Symbol: H3

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).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: at related

Genotype: Bloc1s6pa related

Mammalian Phenotype Terms by Genotype

Genotype: Bloc1s6pa/Bloc1s6painvolves: wild-derived

integument phenotype

pigmentation phenotype

vision/eye phenotype

Genotype: Bloc1s6pa/Bloc1s6paB6.Cg-Bloc1s6/J

behavior/neurological phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

pigmentation phenotype

renal/urinary system phenotype

respiratory system phenotype

vision/eye phenotype

cellular phenotype

growth/size/body region phenotype

Genotype: Bloc1s6pa/Bloc1s6paNot Specified

cellular phenotype

mammalian phenotype

Genotype: a/a Bloc1s6pa/Bloc1s6painvolves: C57BL/6J

pigmentation phenotype

vision/eye phenotype

References

Additional References

Additional - at related

Additional - Bloc1s6pa related

Additional - H3 related

Genotyping Protocols

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

Bloc1s6^pa

Allele Symbol: Bloc1s6^pa

a^t

Allele Symbol: a^t

Genotype: a^t related

Genotype: Bloc1s6^pa related

Genotype: Bloc1s6^pa/Bloc1s6^pa
involves: wild-derived

Genotype: Bloc1s6^pa/Bloc1s6^pa
B6.Cg-Bloc1s6/J

Genotype: Bloc1s6^pa/Bloc1s6^pa
Not Specified

Genotype: a/a Bloc1s6^pa/Bloc1s6^pa
involves: C57BL/6J

Additional - a^t related

Additional - Bloc1s6^pa related