NOD.Cg-Prkdc^scid Tg(Ins2-CD86)12B70Flv/FswJ

Stock number: 007840
Product name: NOD.RIP-CD86
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

These transgenic mice express the human CD86 T cell co-stimulatory protein under the control of the rat insulin promoter (Ins2). Human CD86 mRNA expression is observed in the pancreas. Homozygous transgenic mice lack functional T cells and B cells, and do not become diabetic.

Detailed description

Tg(Ins2-CD86)12B7 mice homozygous for the Prkdc^scid mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Transgenic mice express the human CD86 T cell co-stimulatory protein under the control of the rat insulin promoter (Ins2). RT-PCR analysis detects human CD86 mRNA expression in the pancreas. Very low expression levels are also detected in the kidney and thymus of some but not all transgenic mice. Immunohistochemistry indicates that transgenic CD86 protein expression is restricted to the Islets of Langerhans. Transgenic, Prkdc^scid homozygous mice lack functional T cells and B cells, and do not become diabetic.

In the absence of the Prkdc^scid mutation, NOD-Tg(Ins2-CD86), transgenic mice experience accelerated diabetes. Diabetes onset in male and female transgenic NOD-Tg(Ins2-CD86) mice starts at 8 weeks of age and 85-90% of the mice ultimately become diabetic. Disease progression, however, is not as rapid as in congenic NOD-Tg(Ins2-CD80) transgenic mice.. Both CD80 and CD86 cause accelerated diabetes on the NOD background but there appeared to be a "stronger" effect of CD80. Paradoxically, however, when cells from both diabetic transgenic strains are used in adoptive transfer, the cells from the more accelerated diabetic Tg(Ins2-CD80) stock are far less able to adoptively transfer diabetes to the host than are those from the slower, but still accelerated, Tg(Ins2-CD86) diabetic stock.

These Prkdc^scid homozygous Tg(Ins2-CD86) hemizyous mice are useful for adoptive transfer experiments and as a source of insulitis free pancreatic islets.

Development

A transgenic construct containing the human CD86 gene driven by the rat insulin promoter (RIP) was injected into fertilized (C57BL/6XCBA/Ca)F2 embryos. Founder animals were initially bred to C57BL/6. Resulting progeny of founder 12B70 were backcrossed to NOD for 14 generations prior to mating to NOD.CB17-Prkdc^scid mice. In 2007, The Jackson Laboratory received this mice homozygous for the Prkdc^scid mutation and Tg/? at generation N14F?. The Jackson Laboratory backcrossed the mice received with NOD.CB17-Prkdc^scid/J (Stock No. 001303) prior to sibling mating.

Allele

Symbol: Tg(Ins2-CD86)12B70Flv
Name: transgene insertion 12B70, Richard Flavell
MGI accession ID: MGI:3764558
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Ins2-CD86)12B70Flv
Marker name: transgene insertion 12B70, Richard Flavell
Chromosome: UN
Strain of origin: (C57BL/6 x CBA/Ca)F2
Expressed genes: CD86,CD86 molecule,human
Molecular note: The transgenic construct contains the human CD86 gene driven by the rat insulin 2 promoter (RIP). Transgenic protein expression is restricted to the Islets of Langerhans.

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*).