Overview

Genetic overview

Genetic Background	Generation

Atp7a^Mo-br

Allele Type	Gene Symbol	Gene Name
Spontaneous	Atp7a	ATPase, Cu++ transporting, alpha polypeptide

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Research Applications

Metabolism Research
Dermatology Research
Developmental Biology Research
Neurobiology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Heterozygous females carrying the brindled allele (Atp7a^Mo-br) are very similar to mottled heterozygous females (Atp7a^Mo/+) in appearance but have normal viability. They have curly vibrissae, but the coat is not noticeably waved. Hemizygous males are almost devoid of pigment except in the eyes and ears. The vibrissae are strongly curled, and the coat is wavy. Males usually die by two weeks of age, but a few have lived and been fertile. They have a behavioral abnormality consisting of a slight tremor, uncoordinated gait, and clasping of the hindfeet when held up by the tail. Histological examination of the brain of brindled males shows widespread neuronal degeneration in the cerebral cortex and thalamic nuclei and scattered degeneration in the cerebellum. Heterozygous females have been shown to have neurochemical abnormalities as well. In contrast to mice bearing other Atp7a alleles, brindled mice have no aortic lesions and no defect in crosslinking of collagen and elastin. Brindled males have defective placental transport and defective intestinal absorption of copper. Parenteral injection of copper at 7 to 10 days of age prevents tremor and early death, allows normal pigmentation, improves growth, produces normal concentrations of copper in organs previously deficient (except liver), producesnormal activity of some copper-dependent enzymes, and prevents neuronal degeneration.

Development

Brindled (Atp7a^Mo-br) arose spontaneously in the C57BL strain about 1953 (Fraser, A.S. et al. 1953. J Genetics 51:217-221). It was imported into the Jackson Laboratory on the C57BL/6J background in 1995 from Christine Peterson at The Andrus Gerontology Center of the University of Southern California. Female heterozygotes were bred to C57BL/6J and their female heterozygous offspring were again backcrossed to C57BL/6J before hysterectomy rederivation. This strain is maintained by mating a heterozygous brindled female to a C57BL/6J male each generation. In 2000 this strain reached generation +N11 and in 2006 it reached generation +N25.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Atp7a^Mo-br

Allele Symbol: Atp7a^Mo-br

Allele Name	brindled
Allele Type	Spontaneous
Allele Synonym(s)	Br; Mo^br
Gene Symbol and Name	Atp7a, ATPase, Cu++ transporting, alpha polypeptide
Gene Synonym(s)
Strain of Origin	C57BL
Chromosome	X
General Note	Heterozygous females are very similar to Atp7a^Mo/+ females in appearance but have normal viability. They have curly vibrissae, but the coat is not noticeably waved. Hemizygous males are almost devoid of pigment except in the eyes and ears. The vibrissae are strongly curled, and the coat is wavy. The abnormalities of hair structure have been described by Gr\"uneberg (J:5137).Males usually die when 2 weeks old, but a few have lived and been fertile. They have a behavioral abnormality consisting of a slight tremor, uncoordinated gait, and clasping of the hindfeet when held up by the tail (J:249, J:164). Females homozygous for Atp7a^Mo-br, and also heterozygous Atp7a^Mo-br/Atp7a^Mo and Atp7a^Mo-br/Atp7a^Mo-to females are identical in phenotype to hemizygous Atp7a^Mo-br males and die at the same age (J:164, J:12963).Histological examination of the brain of brindled males shows widespread neuronal degeneration in the cerebral cortex and thalamic nuclei and scattered degeneration in the cerebellum (J:6113). Heterozygous females have been shown to have neurochemical abnormalities as well (J:2026). In contrast to mice bearing other Atp7a alleles, brindled mice have no aortic lesions (J:12963) and no defect in crosslinking of collagen and elastin. Brindled males do, however, have a 30 to 40% reduction in lysyl oxidase activity in skin (J:5777). They have reduced synthesis of noradrenalin by dopamine-ß-hydroxylase in the brain and peripheral nervous system (J:5323), and decreased activity of cytochrome C oxidase and superoxide dismutase (J:5830). These enzymes are all copper-dependent or copper-containing, and their reduced activity may be due to defective copper transport in cells of all affected tissues (J:5956, J:617, J:5747, J:12937).Brindled males have defective placental transport and defective intestinal absorption of copper. Copper concentration is high in gut mucosa, kidney, and testis and low in liver, brain, plasma, and most other organs (J:6204, J:6206). Concentration of the copper-binding protein metallothionein in various tissues is correlated with the concentration of copper (J:7370); however, hepatic metallothionein is inducible at normal levels in mutant neonates (J:24041). Parenteral injection of copper at 7 to 10 days of age has a striking therapeutic effect; it prevents tremor and early death, allows normal pigmentation, improves growth, produces normal concentrations of copper in organs previously deficient (except liver), produces normal activity of some copper-dependent enzymes (J:6205, J:7521), and prevents neuronal degeneration (J:6544). In heterozygotes with tabby (Eda), Atp7a^Mo-br resembles Atp7a^Mo-blo, and thus appears to act on coat color through an effect in hair follicles (J:5238).
Molecular Note	Two significant nucleotide changes were noted in the brindled mouse. A 6 bp in-frame deletion in exon 11 removed a leucine and an alanine at positions 801 and 802 (or 800 and 801, depending on the splice variant) from the encoded protein. A G-to-A transition mutation was also detected at codon 514 (or 513) that changed an alanine codon to threonine, but this alteration is in a region unlikely to affect function. The deletion is in a region postulated to affect Cu transport activity. Western blot analysis demonstrated that a normal sized protein was made from this allele at levels comparable to wild-type.

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).

Menkes disease

Research Areas By Phenotype

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

Genotype: Atp7a^Mo-br related

Metabolism Research
Dermatology Research
- Color and White Spotting Defects
Developmental Biology Research
- Defects in Extracellular Matrix Molecules
Neurobiology Research
- Metabolic Defects
Mouse/Human Gene Homologs
- Menkes syndrome

Mammalian Phenotype Terms by Genotype

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

Genotype: Atp7a^Mo-br/Y
involves: C57BL

homeostasis/metabolism phenotype

abnormal liver copper level
- 7-10 day-old males have significantly reduced (by >2-fold) liver copper levels

abnormal noradrenaline level
- brain levels are reduced by 66% compared to wild-type males

decreased brain copper level
- copper levels in brain are reduced by 40%

decreased circulating copper level
- significant reduction in serum copper (mostly found in ceruplasmin) in males is observed

increased intestine copper level
- 7-10 day-old males show an accumulation of copper in the intestinal wall

liver/biliary system phenotype

abnormal liver copper level
- 7-10 day-old males have significantly reduced (by >2-fold) liver copper levels

nervous system phenotype

abnormal noradrenaline level
- brain levels are reduced by 66% compared to wild-type males

decreased brain copper level
- copper levels in brain are reduced by 40%

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

Genotype: Atp7a^Mo-br/Y
C57BL/6-Atp7a/J

homeostasis/metabolism phenotype

abnormal enzyme/coenzyme activity
- specific activity of superoxide dismutase 3 (SOD3) in fibroblasts is markedly reduced compared to wild-type cells

References

Additional References

Evans GW; Reis BL. 1978. Impaired copper homeostasis in neonatal male and adult female Brindled (Mobr) mice. J Nutr 108(4):554-60PubMed: 564942 MGI: J:5956
Kiaei M; Bush AI; Morrison BM; Morrison JH; Cherny RA; Volitakis I; Beal MF; Gordon JW. 2004. Genetically decreased spinal cord copper concentration prolongs life in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci 24(36):7945-50PubMed: 15356208 MGI: J:92633
Martin PM; Irino M; Suzuki K; Lewis MH; Mailman RB. 1991. The female brindled mouse as a model of Menkes' disease: the relationship of fur pattern to behavioral and neurochemical abnormalities. Dev Neurosci 13(3):121-9PubMed: 1752214 MGI: J:2026

Additional - Atp7a^Mo-br related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

As hemizygous (Atp7a^Mo-br/Y) males and homozygous (Atp7a^Mo-br/Atp7a^Mo-br)females do not survive to breeding age, this strain must be maintained by breeding heterozygous (Atp7a^Mo-br/+) females to wild-type males.
- Additional Breeding and Husbandry Support
Appearance
- black coat with light patches, curly vibrissae
  Related Genotype: a/a Atp7a^Mo-br/+
  
  black
  Related Genotype: a/a +/Y or a/a +/+
Citation
When using the C57BL/6-Atp7a^Mo-br/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #002566 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
	Heterozygous and wildtype females and Hemi or Non Carrier males for Atp7a<Mo-br>

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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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General Terms and Conditions

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Licensing Information

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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Atp7aMo-br

Allele Symbol: Atp7aMo-br

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: Atp7aMo-br related

Mammalian Phenotype Terms by Genotype

Genotype: Atp7aMo-br/Yinvolves: C57BL

homeostasis/metabolism phenotype

liver/biliary system phenotype

nervous system phenotype

Genotype: Atp7aMo-br/YC57BL/6-Atp7a/J

homeostasis/metabolism phenotype

References

Additional References

Additional - Atp7aMo-br 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Atp7a^Mo-br

Allele Symbol: Atp7a^Mo-br

Genotype: Atp7a^Mo-br related

Genotype: Atp7a^Mo-br/Y
involves: C57BL

Genotype: Atp7a^Mo-br/Y
C57BL/6-Atp7a/J

Additional - Atp7a^Mo-br related