These transgenic mice express the human histocompatibility complex (MHC) class I HLA-A2.1 allele in the absence of mouse H-2Db and Β2m.
Dr. David Serreze, The Jackson Laboratory
Genetic Background | Generation |
---|---|
001976 NOD/ShiLtJ |
|
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
This transgenic NOD mouse model, commonly referred to as NOD.HHD, develops significantly accelerated diabetes onset compared to NOD/ShiLtDvs (NOD) inbred mice.
When transgenic mice are bred to NOD-B2m-deficient mice (e.g. Stock No. 002309), which completely lack CD8+ T cells, CD8+ T cells are restored in the double mutant mice, but at significantly lower levels than in NOD inbred mice. FACS analysis indicates that the transgenic NOD-B2m-deficient mice express only the HLA-A2.1/H2-Db chimeric class I molecule. In contrast to NOD.B2mtm1Unc females, which are diabetes free, 55% of the transgenic NOD B2m-deficient females develop diabetes by 30 weeks of age. Insulitis scores determined by histological examination are similar between the NOD double mutant mice and NOD/ShiLtDvs inbred mice, and cultured pancreatic islets from transgenic NOD B2m-deficient mice and from NOD inbred mice produce comparable numbers of CD8+ T cells. Further, the T cells isolated from the transgenic NOD B2m-deficient-derived islet cultures are HLA-A2.1 specific, and are able to recognize islet-specific antigens, such as the Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP).
NOD transgenic mice carrying the Prkdcscid (Stock No. 006605) do not become diabetic.
This model provides humanized T cells that will be a useful tool to identify MHC class I epitopes recognized by CD8+ T cells in type 1 diabetes patients and for testing new therapies focusing on restoring immune tolerance.
This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene and the alpha3, cytoplasmic and transmembrane domains of the murine H2-Db. The transgene was injected into NOD/ShiLtDvs embryos. In 2007, the T1DR received this stock at N1F15. The T1DR mated to NOD/ShiLtJ once prior to sibling mating.
Expressed Gene | B2M, beta-2-microglobulin, human |
---|---|
Expressed Gene | HLA-A, major histocompatibility complex, class I, A, human |
Site of Expression |
Allele Name | transgene insertion 1, David Serreze |
---|---|
Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | HDD; HHD |
Gene Symbol and Name | Tg(HLA-A/H2-D/B2M)1Dvs, transgene insertion 1, David Serreze |
Gene Synonym(s) | |
Promoter | HLA-A2.1, major histocompatibility complex, class I, subtype A2.1, human |
Expressed Gene | B2M, beta-2-microglobulin, human |
Expressed Gene | HLA-A, major histocompatibility complex, class I, A, human |
Strain of Origin | NOD/ShiLtDvs |
Chromosome | UN |
General Note | The HDD construct was created and used to generate a differnet transgenic mouse line in J:41077. |
Molecular Note | This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene, and the alpha3, cytoplasmic and transmembrane domains of the murine H2-Db. The construct was injected into fertilized NOD/ShiLtDvs oocytes. The construct was originally described in J:41077 and used to create a different transgenic line. |
Mutations Made By | Dr. David Serreze, The Jackson Laboratory |
When using the NOD.HHD mouse strain in a publication, please cite the originating article(s) and include JAX stock #006604 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous for Tg(HLA-A/H2-D/B2M)1Dvs |
Frozen Mouse Embryo | NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J Frozen Embryo | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.