STOCK Prkdc^scid Gnrh1^hpg/BmJ

Stock number: 010605
Research areas: Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Reproductive Biology Research, Research Tools, Virology Research

Description

Ghrh^hpg Prkdc^scid double mutant mice are useful for determining endocrine dependence of grafted cells/tissues.

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. Hypogonadal mice (Ghrh^hpg) mice are deficient in gonadotropins and gonodal steroids leading to an overall underdevelopment of the reproductive tract. Male mice have a small penis and scrotum and a short ano-genital distance. All male reproductive organs are present but immature. The testes are small and undescended. Spermatogenesis is arrested, usually by the diplotene stage. The vagina of female mice does not open fully, the uterus is thread-like, and the ovaries very small. Both sexes are sterile although fertility can be restored with hormone replacement. Ghrh^hpg Prkdc^scid double mutant mice are useful for determining endocrine dependence of grafted cells/tissues.

Development

A mouse homozygous for the Prkdc^scid and Igh^b mutations on the CB17/IcrSmn background was bred with an HPG/BmJ mouse and the offspring were intercrossed to generate a line on a segregating background, homozygous for Prkdc^scid and segregating for Gnrh1^hpg. This strain (stock #002038) was maintained by intercrossing siblings homozygous for the scid mutation and heterozygous for the hpg mutation. In 2009, when this strain reached generation F34, sperm were cryopreserved from a male homozygous for scid and heterozygous for hpg. Cryorecovery will use CBySmn.CB17-Prkdc^scid/J females (stock #001803).

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; S473K; 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*).

Allele

Symbol: Gnrh1^hpg
Name: hypogonadal
MGI accession ID: MGI:1856393
Generation method: Spontaneous
Synonyms: Gnrh^-; gnrh^hpg; hpg
Marker symbol: Gnrh1
Marker name: gonadotropin releasing hormone 1
Marker synonyms: Gnrh; Gnrha; GRH; Lhrh; LNRH; Rgnrhg1; SH-4
Chromosome: 14
Strain of origin: C3H101H-Rb(1.3)1Bnr
Molecular note: The mutation in the hypogonadal mouse is an approximately 33.5 kb deletion that removes two exons that encode most of the protein.