NOD.Cg-Emv30^b Prkdc^scid/Dvs

Stock number: 002313
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

Mice homozygous for the severe combined immune deficiency spontaneous mutation (Prkdc^scid, commonly referred to as scid) are characterized by an absence of functional T cells and B cells, lymphopenia, hypogammaglobulinemia, and a normal hematopoietic microenvironment. The NOD.Cg-Prkdc^scid Emv30^b/Dvs strain was produced to test the role of Emv30, an endogenous murine ecotropic retrovirus unique to the NOD genome in thymomagenesis.

Detailed description

Mice homozygous for the severe combined immune deficiency spontaneous mutation (Prkdc^scid, commonly referred to as scid) are characterized by an absence of functional T cells and B cells, lymphopenia, hypogammaglobulinemia, and a normal hematopoietic microenvironment. Normal antigen-presenting cell, myeloid and NK cell functions are strain dependent. scid mice carry a DNA repair defect and a defect in the rearrangement of genes that code for antigen-specific receptors on lymphocytes. Most homozygotes have no detectable IgM, IgG1, IgG2a, IgG2b, IgG3, or IgA. Thymus, lymph nodes, and splenic follicles are virtually devoid of lymphocytes. scid mice accept allogeneic and xenogeneic grafts making them an ideal model for cell transfer experiments. Some scid mice will spontaneously develop partial immune reactivity. scid mice that have serum Ig levels greater than 1 ug/ml are considered "leaky." scid leakiness is highly strain dependent, increases with age, and is higher in mice housed under non SPF conditions. In general, scid leakiness is high on the C57BL/6J and BALB/cBy genetic backgrounds, low on the C3H/HeJ background, and even lower on the NOD/LtSz background. NOD/LtSz-Prkdc^scid mice are both insulitis- and diabetes-free throughout life and serve as a diabetes free control for comparison to NOD/LtJ mice (Stock No. 001976). However, there is a high incidence of thymic lymphomas in this congenic stock limiting the mean lifespan to only 8.5 months under specific pathogen-free conditions. To test the role of Emv30, an endogenous murine ecotropic retrovirus unique to the NOD genome in thymomagenesis, a stock of EMV30 null NOD-Prkdc^scid mice was produced. Thymic lymphomas still initiate in NOD.Cg-Prkdc^scid Emv30^b/Dvs females but the rate of tumor progression is significantly retarded. Also, tumors in this congenic are not characterized by a compensatory increase in mink cell focus-forming proviral integrations, which are important in initiating thymomagenesis in other susceptible mouse strains.

Development

This strain was generated by backcrossing the Emv30^b in the proximal end of Chromosome 11 from a NOR/Lt male, then at generation N9, onto the NOD/Lt strain for five backcross generations then crossing once to the NOD.CB17-Prkdc^scid/J strain, after which the heterozygous offspring were intercrossed to make the line homozygous for Prkdc^scid. This line was further backcrossed five generations to NOD.CB17-Prkdc^scid/J and then sibling intercrossed for homozygosity of both Prkdc^scid and Emv30^b and maintained by continuous sibling intercrossing.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
Molecular note: A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*).

Allele

Symbol: Emv30^b
Name: endogenous ecotropic murine leukemia virus, absent
MGI accession ID: MGI:1857806
Generation method: Not Applicable
Marker symbol: Emv30
Marker name: endogenous ecotropic MuLV 30
Chromosome: 11
Strain of origin: Not Applicable
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).