These mutant mice combine the immunological characteristics of the NOD/ShiLtJ background, the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency and a hypoxanthine phosphoribosyl transferase (Hprtb-m3) null allele. This mutant mouse strain may be useful for xenotransplantation and drug screening.
James Eshleman, John Hopkins UniversityRead More +
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Hprt||hypoxanthine guanine phosphoribosyl transferase|
|Allele Type||Gene Symbol||Gene Name|
|Targeted (Null/Knockout)||Il2rg||interleukin 2 receptor, gamma chain|
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Prkdc||protein kinase, DNA activated, catalytic polypeptide|
Mice that are homozygous/hemizygous for these alleles are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mutant mice combine the following characteristics: NK cell deficiency (NOD/ShiLtJ background), T and B cell deficiency (Prkdcscid), reduced numbers of lymphocytes and myeloid dendritic cells (Il2rgtm1Wjl) and biochemically defective stromal cells (Hprtbm-3). These mice can be used for transplantation of human primary cancers. During tumor growth, Hprt-defective murine fibroblast and stromal cells replace human stromal cells. In culture, the addition of HAT selection media eliminates murine fibroblasts and other stromal cells and facilitates the isolation of human cancer cells. These mice may be used to generate patient-specific low passage cell lines from primary cancers for use in chemosensitivity profiling and other applications.
The Hprtbm-3 allele, a spontaneous 36 kb deletion at the 3' end of exon 2, was selected from an HPRT deficient 129P2/OlaHsd-derived E14TG2a embryonic stem cell line (ES). The X-linked mutation was introgressed into C57BL/6 mice for at least 5 generations. A heterozygous female was crossed to a NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (Stock No. 005557) male; the backcross was continued for five generations. Correctly genotyped pups from each generation were selected using marker assisted genome scan analysis (speed congenic).
|Allele Name||hypoxanthine guanine phosphoribosyl transferase B, mutation 3|
|Gene Symbol and Name||Hprt, hypoxanthine guanine phosphoribosyl transferase|
|Gene Synonym(s)||C81579; HGPRT; HPRT; Hgprtase; Hprt1; Hprt1; expressed sequence C81579; hypoxanthine guanine phosphoribosyl transferase 1|
|Strain of Origin||129P2/OlaHsd|
|General Note||HPRT- embryonic stem cells were obtained by selecting for spontaneous mutation by incubation in medium containing 6-thioguanine. HPRT- males have no overt phenotype of abnormal behavior (J:15483). The mutation is due to a large deletion in the Hprt gene.In situ hybridization studies showed HPRT mRNA in high levels in most neurons, but not in glial cells, in normal mice. No HPRT mRNA was detected in the brains of male mice carrying this deletion (J:2058). Mutant mice have no HPRT detectable by Western blot analysis and no detectable HPRT enzyme activity in brain homogenates. They appear to have normal brain purine content, but de novo purine synthesis is accelerated four- to fivefold (J:11842). The Hprtb-m3 mutation has been used in preimplantation studies to determine when the maternal and paternal alleles of Hprt are activated during early embryonic development (J:2389). Either administration of amphetamine (J:1847) or inhibition of adenine phosphoribosyltransferase (APRT) activity (J:4123) stimulates locomotor and stereotypic behaviors in HPRT-deficient mice. However, the null mutant for both Hprt and Aprt does not show the characteristics of Lesch-Nyhan disease (J:35822).Cells from mice hemizygous or homozygous for this mutation are HPRT-deficient and resistant to the drug 6-thioguanine (6TG).|
|Molecular Note||The allele contains a ~55 kb deletion spanning the promoter and first 2 exons. Subsequent direct sequence comparison with wild type DNA defined the exact breakpoints of the deletion, which lies 415 bp after the 3' end of exon 2, and determined the deletion size to be 36 kb.|
|Mutations Made By|| |
Elizabeth Simpson, Centre for Molecular Medicine & Therapeutics, University of British Columbia
|Allele Name||targeted mutation 1, Warren J Leonard|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD132-; IL2Rgammanull; Il2rgtm1Wjll; [KO]gammac; gammac-; gc-|
|Gene Symbol and Name||Il2rg, interleukin 2 receptor, gamma chain|
|Gene Synonym(s)||Ab2-183; CD132; CIDX; Cd132; IL-2RG; IMD4; P64; SCIDX; SCIDX1; [g]c; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gc|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein.|
|Mutations Made By|| |
Dr. Warren Leonard, NHLBI, NIH
|Allele Name||severe combined immunodeficiency|
|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|
|Strain of Origin||C.B-17|
|Molecular Note||A T-to-A transversion point mutation at a position corresponding to codon 4095 created a premature stop codon.|
When maintaining a live colony, these mice are bred as homozygous for the Prkdcscid allele and homozygous/hemizygous for the X-linked Il2rgtm1Wjl and Hprtb-m3 alleles. SPF (specific pathogen-free) conditions are recommended.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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