NOD.Cg-Prkdc^scid/J

Stock number: 001303
Product name: NOD scid
Strain synonyms: NOD SCID
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. Prkdc^scid mice accept allogeneic and xenogeneic grafts making them an ideal model for cell transfer experiments. In general, Prkdc^scid leakiness is low on the NOD/ShiLtSz genetic background.

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/ShiLtSz background. NOD/ShiLtSz-Prkdc^scid mice are both insulitis- and diabetes-free throughout life and serve as a diabetes-free control for comparison to NOD/ShiLtJ mice (Stock No. 001976). Thymic lymphomas occur with high frequency, however, and life span typically is limited to only 8.5 months under specific pathogen-free conditions. In addition to being an excellent host for xenografts, NOD.CB17-Prkdc^scid/J mice may be useful for delineation of the role of T cell subsets in autoimmune diabetes and also as a source for insulitis-free islets.

View Flow Cytometry Characterization Data for Immunodeficient JAX Strains

Development

Prkdc^scid occurred spontaneously in a colony of BALB/c-Igh^b (C.B-17) mice maintained at the Institute for Cancer Research in Philadelphia, PA. The Prkdc^scid mutation was backcrossed onto the NOD/ShiLtSz background as follows: an NOD/ShiLtSz female was bred to a C.B-17-Prkdc^scid male; male Prkdc^scid/+ offspring of the F1/N1 and subsequent generations were mated to NOD/ShiLt females for a total of 10 crosses to NOD/ShiLtSz; at generation N10, Prkdc^scid was made homozygous by brother-sister inbreeding.

Allele

Symbol: Hc⁰
Name: deficient
MGI accession ID: MGI:3027637
Generation method: Spontaneous
Synonyms: C5-; C5-d; C5-def; C5-deficient; Hc^Hfib2; hc^o
Marker symbol: Hc
Marker name: hemolytic complement
Marker synonyms: C5; C5a; C5b; C5D; CPAMD4; ECLZB; He; Hfib2
Chromosome: 2
Strain of origin: multiple strains
Molecular note: A 2 base "TA" deletion at positions 62 and 63 of an 83 base pair exon near the 5' end of the gene is found in the following mouse strains: A/HeJ, A/J, AKR/J, DBA/2J, I/LnJ, KK/HlJ, MOLF/EiJ, NZB/B1NJ, RF/J, ST/bJ SWR/J, B10.D2/oSnJ. The consequence of this deletion is the creation of a stop codon starting four bases after the deletion. A truncated product of 216 amino acids is predicted as a result although contradictory reports exist that a larger pro-C5 protein may be synthesized. Nevertheless, macrophages from mouse strains carrying this allele do not secrete complement 5.
General note:

This is an allele characteristic of various inbred mouse strains including the following: A/HeJ, A/J, AKR/J, DBA/2J, NZB/B1NJ, SWR/J, B10.D2/oSnJ

Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The A/J allele contains a 2 bp deletion resulting in deficient Hc mRNA and protein production and is associated with susceptibility to allergen-induced bronchial hyperresponsiveness. (J:108211)

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Synonyms: scid
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Marker synonyms: DNAPDcs; DNAPK; DNA-PK; DNAPKc; DNA-PKC; DNA-PKcs; DNPK1; DOXNPH; dxnph; HYRC; HYRC1; IMD26; p350; slip; XRCC7
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*).