Overview

This C57BL/6J congenic strain, commonly called Nramp1^r/r, may be useful to further study the role of the ion transporter Nramp1 in mycobacterial infections.

Donating Investigator

Greg Barton, University of California, Berkeley

Genetic overview

Genetic Background	Generation

Slc11a1^r

Allele Type	Gene Symbol	Gene Name
Not Applicable	Slc11a1	solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Cell Biology Research
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

This C57BL/6J congenic strain, commonly called Nramp1^r/r, contain a genomic segment from the mycobacteria resistant 129S1 background introgressed into Chromosome 1. This segment contains Slc11a1, solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1, also known as Nramp1 (natural-resistance-associated macrophage protein 1) or the Bcg/Ity/Lsh locus. NRAMP1 is a membrane protein expressed on macrophages that acts as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations, resulting in a non-functional protein, have been associated with the innate susceptibility of mice to infection with a group of unrelated intracellular parasites which includes Mycobacterium bovis, Salmonella typhimurium, and Leishmania donovani. The lack of functionality causes an accumulation of ions inside the phagosome, favoring the replication of the pathogens. This strain contains a 129S1-derived natural resistance mutation in the Slc11a1 gene backcrossed onto the infection susceptible C57BL/6J background. A guanine at nucleotide position 783 produces a protein with Glycine at position 105 within the second predicted transmembrane domain. The protein also has Glycine at position 169 within the fourth predicted transmembrane domain. Nramp1^r/r mice are resistant to infection by mycobacterial infections.

Development

This C57BL/6J congenic strain contains a genomic segment from the mycobacteria resistant 129S1 background introgressed into Chromosome 1. The chromosome 1 genomic segment from 129 contains Slc11a1, solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1 (74.3Mb). A guanine mutation at nucleotide position 783 produces a protein with Glycine at position 105 within the second predicted transmembrane domain. The protein also has Glycine at position 169 within the fourth predicted transmembrane domain. The 129S1 genomic segment was transferred through 12 generations of backcrossing to C57BL/6J. Siblings carrying the 129S1 derived segments were intercrossed to make homozygous.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Arpaia N; Godec J; Lau L; Sivick KE; McLaughlin LM; Jones MB; Dracheva T; Peterson SN; Monack DM; Barton GM. 2011. TLR signaling is required for Salmonella typhimurium virulence. Cell 144(5):675-88PubMed: 21376231 MGI: J:217523
Sivick KE; Arpaia N; Reiner GL; Lee BL; Russell BR; Barton GM. 2014. Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies. Cell Host Microbe 15(2):203-13PubMed: 24528866 MGI: J:217577

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Genetics

Slc11a1^r

Allele Symbol: Slc11a1^r

Allele Name	host resistance (Bcg/Ity/Lsh)
Allele Type	Not Applicable
Allele Synonym(s)	Bcg^r; Lsh^r; Nramp1^G169; Nramp1^Gly169; Slc11a1^Bcg; Slc11a1^Ity; Slc11a1^Lsh; Slc11a1^rs47476426-G
Gene Symbol and Name	Slc11a1, solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1
Gene Synonym(s)
Strain of Origin	multiple strains
Chromosome	1
General Note	Multiple genes may be involved in the control of mycobacterial infections in inbred mice (J:17780); the early phase of these infections is controlled in Slc11a1^r strains, but later phases are not (J:28278). The point mutation associated with the susceptible phenotype (Slc11a1^s) was initially identified as Gly105Arg. In J:25627 (1995), the authors report that the full-length mRNA encodes a protein 64 amino acids longer at the N-terminus than previously reported, including two additional transmembrane domains. Therefore, the actual amino acid substitution is Gly169Arg, and the resistant allele Gly169 (or G169). The nucleotides cannot be assigned numbers because the gene contains no TATA or CAAT element and has multiple transcription initiation sites. (J:25627) Resistant strains include 129S4/SvJae, 129X1/SvJ, A/J, AKR/J, BUB/BnJ, C3H/HeJ, C57BR/cdJ, C57L/J, C58/J, CBA/J, DBA/2J, LP/J, NOD/ShiLt, NZB/BlNJ, P/J, PL/J, RIIIS/J, RF/J, SJL/J, SWR/J, Mus spretus (Spain). (J:4762, J:20139) Some of these strains carry silent nucleotide substitutions. (J:20139)
Molecular Note	Natural resistance to infection with diverse pathogens, including some Mycobacterium species, Salmonella typhimurium, and Leishmania donovani, is associated with a protein having glycine at amino acid position 169, within the fourth predicted transmembrane domain (G169 or Gly169). This glycine is evolutionarily conserved in rat, human, rabbit and chicken orthologous proteins. G169 is associated with the G variant of SNP rs47476426 and is found in 129P2/OlaHsd, 129S1/SvImJ, 129S5SvEvBrd, C3H/HeJ and most other strains. Reference strain C57BL/6, and BALB/cJ and FVB/NJ have the A variant of the SNP, coding for aspartic acid at position 169, that causes sensitivity.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
Cell Biology Research
- Channel and Transporter Defects
Metabolism Research
- Iron Metabolism

Mammalian Phenotype Terms by Genotype

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

Genotype: Slc11a1^r/Slc11a1^r
C3H/HeJ-Slc11a1

immune system phenotype

decreased susceptibility to bacterial infection
- little or no bacterial proliferation in the spleen at any time following BCG inoculation
- increased resistance to mycobacterial infection during the early but not the late phase of acquired immunity

Genotype: Slc11a1^r/Slc11a1^r
129/Sv

immune system phenotype

decreased susceptibility to bacterial infection
- spleen bacterial loads in mice infected with 10³ Salmonella CFUs increased steadily from day 1 until day 7, then declined sharply by day 21, and were almost undetectable by day 42 postinfection
- increased resistance to mycobacterial infection during the early but not the late phase of acquired immunity

References

Arpaia N; Godec J; Lau L; Sivick KE; McLaughlin LM; Jones MB; Dracheva T; Peterson SN; Monack DM; Barton GM. 2011. TLR signaling is required for Salmonella typhimurium virulence. Cell 144(5):675-88PubMed: 21376231 MGI: J:217523
Sivick KE; Arpaia N; Reiner GL; Lee BL; Russell BR; Barton GM. 2014. Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies. Cell Host Microbe 15(2):203-13PubMed: 24528866 MGI: J:217577

Additional - Slc11a1^r related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Slc11a1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6J.129S1-Slc11a1^r/GbrtJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #027081 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 for Slc11a1<r>

Payment Terms and Conditions

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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

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Slc11a1r

Allele Symbol: Slc11a1r

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Slc11a1r/Slc11a1rC3H/HeJ-Slc11a1

immune system phenotype

Genotype: Slc11a1r/Slc11a1r129/Sv

immune system phenotype

References

Additional - Slc11a1r related

Genotyping Protocols

Breeding Considerations

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

Additional Use Restrictions Apply

Licensing Information

Slc11a1^r

Allele Symbol: Slc11a1^r

Genotype: Slc11a1^r/Slc11a1^r
C3H/HeJ-Slc11a1

Genotype: Slc11a1^r/Slc11a1^r
129/Sv

Additional - Slc11a1^r related