JAX Mouse Strain Datasheet - 006605

NOD.Cg-Prkdc^scid Emv30^b Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ

Stock No:: 006605 |; NOD.scid HHD

Cryo Recovery

Overview

Also Known As: NOD.scid HHD

These multiple mutant mice express the human histocompatibility complex (MHC) class I HLA-A2.1 allele in the absence of mouse H-2D^b, Β2m, and endogenous ecotropic murine leukemia virus (Emv30^b).

Donating Investigator

Dr. David Serreze, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
002313 NOD.Cg-Prkdc^scid Emv30^b/Dvs

Emv30^b

Allele Type	Gene Symbol	Gene Name
Not Applicable	Emv30	endogenous ecotropic MuLV 30

Prkdc^scid

Allele Type	Gene Symbol	Gene Name
Spontaneous	Prkdc	protein kinase, DNA activated, catalytic polypeptide

Tg(HLA-A/H2-D/B2M)1Dvs

Allele Type
Transgenic (Humanized sequence, Inserted expressed sequence)

View Genetics

Research Applications

Diabetes and Obesity Research
Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research
Virology Research

View All Research Applications

Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Although NOD mice that carry this transgene (Stock No. 006604) develop diabetes significantly earlier than do NOD/ShiLtDvs (NOD) controls, this transgenic strain harbors the Prkdc^scid mutation (characterized by an absence of functional T cells and B cells), and therefore does not become diabetic. This strain is useful for adoptive transfer experiments, and as a source of insulitis free pancreatic islets.

Development

This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene and the alpha3, cytoplasmic and transmembrane domains of the murine H2-D^b protein. The transgene was injected into NOD/ShiLtDvs embryos. Transgenic offspring were mated to NOD.Prkdc^scid Emv30^b (Stock No. 002313), prior to sibling mating and fixing for homozygosity. In 2007, the T1DR received this stock at generation N2F2.

Expression Data

Expressed Gene	B2M, beta-2-microglobulin, human
Expressed Gene	HLA-A, major histocompatibility complex, class I, A, human
Site of Expression

Control Suggestions

Additional Information

Considerations for Choosing Controls

Selected References

Pascolo S; Bervas N; Ure JM; Smith AG; Lemonnier FA; Perarnau B. 1997. HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 185(12):2043-51. PubMed: 9182675 MGI: J:41077
Takaki T; Marron MP; Mathews CE; Guttmann ST; Bottino R; Trucco M; DiLorenzo TP; Serreze DV. 2006. HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J Immunol 176(5):3257-65. PubMed: 16493087 MGI: J:121685

View All References

Genetics

Emv30^b

Allele Symbol: Emv30^b

Allele Name	endogenous ecotropic murine leukemia virus, absent
Allele Type	Not Applicable
Allele Synonym(s)
Gene Symbol and Name	Emv30, endogenous ecotropic MuLV 30
Gene Synonym(s)	Emv-30; Emv-30
Strain of Origin	Not Applicable
Chromosome	11
General Note	The provirus is missing from C57BLKS/J and from the NOR/LtDn stock which was derived from an NOD subline genetically contaminated with C57BLKS/J (J:14300, J:29951).

Prkdc^scid

Allele Symbol: Prkdc^scid

Allele Name	severe combined immunodeficiency
Allele Type	Spontaneous
Allele Synonym(s)	SCID; scid
Gene Symbol and Name	Prkdc, protein kinase, DNA activated, catalytic polypeptide
Gene Synonym(s)	AI326420; AU019811; DNA-PK; DNA-PKcs; DNAPDcs; DNAPK; DNPK1; DOXNPH; HYRC; HYRC1; IMD26; XRCC7; doxorubicin nephropathy; dxnph; dxnph; expressed sequence AI326420; expressed sequence AU019811; p350; scid; severe combined immunodeficiency; slip
Site of Expression	T and B lymphocytes.
Strain of Origin	C.B-17
Chromosome	16
Molecular Note	A T-to-A transversion point mutation at a position corresponding to codon 4095 created a premature stop codon.

Tg(HLA-A/H2-D/B2M)1Dvs

Allele Symbol: Tg(HLA-A/H2-D/B2M)1Dvs

Allele Name	transgene insertion 1, David Serreze
Allele Type	Transgenic (Humanized sequence, Inserted expressed sequence)
Allele Synonym(s)	HDD; HHD
Gene Symbol and Name	Tg(HLA-A/H2-D/B2M)1Dvs, transgene insertion 1, David Serreze
Gene Synonym(s)	HDD; HHD
Promoter	HLA-A2.1, major histocompatibility complex, class I, subtype A2.1, human
Expressed Gene	B2M, beta-2-microglobulin, human
Expressed Gene	HLA-A, major histocompatibility complex, class I, A, human
Strain of Origin	NOD/ShiLtDvs
Chromosome	UN
General Note	The HDD construct was created and used to generate a differnet transgenic mouse line in J:41077.
Molecular Note	This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene, and the alpha3, cytoplasmic and transmembrane domains of the murine H2-D^b. The construct was injected into fertilized NOD/ShiLtDvs oocytes. The construct was originally described in J:41077 and used to create a different transgenic line.
Mutations Made By	Dr. David Serreze, The Jackson Laboratory

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Diabetes and Obesity Research
- Islet Transplantation Studies
- Type 1 Diabetes (IDDM) Analysis Strains
  - NOD Congenics with Mutations Affecting Immunocompetence
  - NOD Transgenics
Immunology, Inflammation and Autoimmunity Research
- HLA transgenics
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency, xenograft/transplant host

Genotype: Prkdc^scid related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Research Tools
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
- Toxicology Research
  - xenograft/transplant host
Virology Research
- B and T Cell Deficiency
  - AIDS research tool

References

Pascolo S; Bervas N; Ure JM; Smith AG; Lemonnier FA; Perarnau B. 1997. HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 185(12):2043-51. PubMed: 9182675 MGI: J:41077
Takaki T; Marron MP; Mathews CE; Guttmann ST; Bottino R; Trucco M; DiLorenzo TP; Serreze DV. 2006. HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J Immunol 176(5):3257-65. PubMed: 16493087 MGI: J:121685

Additional References

Taylor BA; Rowe L; Grieco DA. 1993. The MEV mouse linkage testing stock: mapping 30 novel proviral insertions and establishment of an improved stock. Genomics 16(2):380-94. PubMed: 8390965 MGI: J:4958

Additional - Emv30^b related

Marron MP; Graser RT; Chapman HD; Serreze DV. 2002. Functional evidence for the mediation of diabetogenic T cell responses by HLA-A2.1 MHC class I molecules through transgenic expression in NOD mice. Proc Natl Acad Sci U S A 99(21):13753-8. PubMed: 12361980 MGI: J:109851
Prochazka M; Gaskins HR; Leiter EH. 1991. Emv-30: a novel ecotropic MuLV present in NOD/Lt and NON/Lt strains. Mouse Genome 89:258. MGI: J:14300
Serreze DV; Leiter EH; Hanson MS; Christianson SW; Shultz LD; Hesselton RM; Greiner DL. 1995. Emv30null NOD-scid mice. An improved host for adoptive transfer of autoimmune diabetes and growth of human lymphohematopoietic cells. Diabetes 44(12):1392-8. PubMed: 7589844 MGI: J:29951

Additional - Prkdc^scid related

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Additional - Tg(HLA-A/H2-D/B2M)1Dvs related

Chen X; Tang Y; Zhang Y; Zhuo M; Tang Z; Yu Y; Zang G. 2014. Tapasin modification on the intracellular epitope HBcAg18-27 enhances HBV-specific CTL immune response and inhibits hepatitis B virus replication in vivo. Lab Invest 94(5):478-90. PubMed: 24614195 MGI: J:208402
Enee E; Martinuzzi E; Blancou P; Bach JM; Mallone R; van Endert P. 2008. Equivalent specificity of peripheral blood and islet-infiltrating CD8+ T lymphocytes in spontaneously diabetic HLA-A2 transgenic NOD mice. J Immunol 180(8):5430-8. PubMed: 18390725 MGI: J:134255
Jaiswal S; Pearson T; Friberg H; Shultz LD; Greiner DL; Rothman AL; Mathew A. 2009. Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice. PLoS One 4(10):e7251. PubMed: 19802382 MGI: J:154110
Jarchum I; Baker JC; Yamada T; Takaki T; Marron MP; Serreze DV; DiLorenzo TP. 2007. In vivo cytotoxicity of insulin-specific CD8+ T-cells in HLA-A*0201 transgenic NOD mice. Diabetes 56(10):2551-60. PubMed: 17620420 MGI: J:126569
Jarchum I; DiLorenzo TP. 2010. Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin. J Immunol 184(2):658-65. PubMed: 19966211 MGI: J:159429
Niens M; Grier AE; Marron M; Kay TW; Greiner DL; Serreze DV. 2011. Prevention of 'Humanized' diabetogenic CD8 T-cell responses in HLA-transgenic NOD mice by a multipeptide coupled-cell approach. Diabetes 60(4):1229-36. PubMed: 21346176 MGI: J:171756
Serreze DV; Marron MP; Dilorenzo TP. 2007. 'Humanized' HLA transgenic NOD mice to identify pancreatic beta cell autoantigens of potential clinical relevance to type 1 diabetes. Ann N Y Acad Sci 1103:103-11. PubMed: 17376821 MGI: J:123948
Shultz LD; Saito Y; Najima Y; Tanaka S; Ochi T; Tomizawa M; Doi T; Sone A; Suzuki N; Fujiwara H; Yasukawa M; Ishikawa F. 2010. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice. Proc Natl Acad Sci U S A 107(29):13022-7. PubMed: 20615947 MGI: J:162315
Tsai S; Shameli A; Yamanouchi J; Clemente-Casares X; Wang J; Serra P; Yang Y; Medarova Z; Moore A; Santamaria P. 2010. Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity 32(4):568-80. PubMed: 20381385 MGI: J:179859
Whitfield-Larry F; Young EF; Talmage G; Fudge E; Azam A; Patel S; Largay J; Byrd W; Buse J; Calikoglu AS; Shultz LD; Frelinger JA. 2011. HLA-A2-matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/gammac(null)/HLA-A2 transgenic mice concurrent with the expansion of islet-specific CD8+ T cells. Diabetes 60(6):1726-33. PubMed: 21521873 MGI: J:177952

Also Known As: NOD.scid HHD

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Emv30b

Allele Symbol: Emv30b

Prkdcscid

Allele Symbol: Prkdcscid

Tg(HLA-A/H2-D/B2M)1Dvs

Allele Symbol: Tg(HLA-A/H2-D/B2M)1Dvs

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Genotype: Prkdcscid related

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Emv30^b

Allele Symbol: Emv30^b

Prkdc^scid

Allele Symbol: Prkdc^scid

Genotype: Prkdc^scid related

Additional - Emv30^b related

Additional - Prkdc^scid related