Newly Available JAX® GEMM® Strains
JAX® NOTES Issue 503, Fall 2006
We are pleased to announce that we are now distributing the following JAX® GEMM® (Genetically Engineered and Mutant Mice) strains.
For ordering information, please contact Customer Service by e-mail at orderquest@jax.org or call 800.422.MICE (6423) or 207.288.5845.
B6;FVB-Tg(Pcp2-EGFP)2Yuza/J (004690)
These transgenic mice express enhanced green fluorescent protein (EGFP) under the direction of the mouse Purkinje cell protein 2 (Pcp2) promoter. Hemizygotes are viable, fertile, and look and behave normally. They express EGFP in dendrites, axons, and soma of Purkinje cells, allowing investigators to identify, isolate, and purify Purkinje cells by FACS. Their EGFP expression pattern mimics that of endogenous Purkinje cell protein 2. Fluorescence is detectable at embryonic day 17 in Purkinje cells and also occurs in retinal bipolar cells. Low levels of fluorescence are seen in olfactory periglomerular cells, interpeduncular nucleus, and superior colliculus neurons. This strain may be useful for purifying and tracking Purkinje cells in vivo.
STOCK Tg(ACTB-DsRed.MST)1Nagy/J (005441)
Mice homozygous for the transgenic insert are viable, fertile, and look and behave normally. They express the red fluorescent protein variant DsRed.MST under the control of the chicken beta actin promoter coupled with the cytomegalovirus (CMV) immediate early enhancer. All tissues of homozygotes fluoresce red. Tissues in hemizygotes fluoresce less intensely. Expression is observed throughout all embryonic and adult stages and is very high in pancreas, skeletal muscle, heart, and seminal vesicle.
B6.129S1-Card15tm1Flv/J (005763)
Homozygotes for this targeted mutation of the caspase recruitment domain family, member 15 (Card15) gene are viable, fertile, and do not show histological evidence of intestinal inflammation up to six months of age. Normally, Card15 is expressed in myeloid cells and intestinal crypts, where it plays an integral role in intestinal immunity. Thymus and spleen of the Card15 knockouts have normal lymphoid and myeloid cellularity. Macrophages and dendritic cells deficient in Card15 expression do not recognize muramyl dipeptide (MDP), a conserved structure in bacterial peptidoglycan. When macrophages and dendritic cells from mutant mice are challenged with MDP in vitro, they are unable to produce IL-6, IL-12p40, and NF-kappaB. Mutant mice challenged in vivo with MDP are unable to mount an adaptive immune response, indicated by lack of IgG1 production. These mice have decreased expression of cryptdins, which are important in innate immune responses following bacterial infection. These mice also show increased susceptibility to oral (intragastric) bacterial challenge. They may be useful for researching Crohn's disease and other inflammatory bowel diseases, innate immunity, signal transduction, and bacterial susceptibility.
B6.Cg-Tg(Cd4-TGFBR2)16Flv/J (005551)
These transgenic mice express a dominant-negative form of the human transforming growth factor, beta receptor II (dnTGFBRII) driven by the mouse CD4 antigen promoter. Transgene expression is detected by RT-PCR analysis of thymus tissue, and is sufficient to block TGF-beta signaling in CD4+ and CD8+ T cells. Between three and four months of age, transgenic mice begin to waste and have diarrhea. Histological examination reveals inflammatory bowel disease (IBD) and inflammatory infiltration of the large intestine, lungs, and liver. Less severe infiltration is observed in the stomach, duodenum, pancreas, and kidney. The donating investigator indicates that the severity of IBD and the organs affected is influenced by strain background. Western blot analysis detects circulating autoreactive antibodies. IgG immune deposits form in kidney glomeruli. There is a three-fold increase in total cell numbers in peripheral lymphoid organs. T cells spontaneously differentiate into Th1 or Th2 cytokine secreting cells. These mice do not develop tumors when challenged with TGF-beta producing tumor cells. Hemizygotes are viable and fertile. Hemizygous females do not support pregnancies well. This strain may be useful for researching autoimmune disease, anti-tumor immune response, and inflammatory bowel disease.
B6.FVB-Tg(ITGAM-DTR/EGFP)34Lan/J (006000)
Homozygotes for this transgene are viable and look and behave normally. The transgene is a diphtheria toxin (DT) inducible system that transiently depletes specific macrophage subpopulations. It contains a fusion product involving simian diphtheria toxin receptor and green fluorescent protein under the control of the human ITGAM (integrin alpha M) promoter (CD11b). The murine DT receptor binds DT poorly, allowing cells that do not express CD11b to escape ablation. Twelve hours following a single intraperitoneal (IP) injection of DT, all F4/80 positive macrophages are cleared from the peritoneum and are restored four days later. Peripheral blood polymorphonuclear cells are not depleted, but the majority of circulating monocytes are depleted. Mice given two IP injections of DT showed depletion of F4/80 positive macrophages in kidney and ovary, but hepatic and alveolar macrophages remained. DT doses greater than 25ng/g body weight sicken the mice. This strain may be useful for researching the role of macrophages in the immune response.
B6.129P2-P2rx7tm1Gab/J (005576)
Homozygotes for this targeted mutation of the P2X purinergic, ligand-gated ion channel 7 (P2rx7) receptor gene are viable, fertile, and look and behave normally. P2rx7 is normally expressed by monocytes, macrophages, microglial cells and lymphocytes. Neither cultured bone marrow mast cells nor peritoneal macrophages from these mutants produce a detectable gene product (mRNA or protein). When P2rx7 is activated with ATP in wild type cells, it transforms into a cell membrane pore that allows passage of molecules as large as 900 Da. Myeloid cells stimulated with lipopolysaccharide (LPS) produce proIL-1β, but biologically active IL-1β is not released from these cells until P2rx7 is activated with ATP. Consequently, myeloid cells from the mutant animals have poor inflammatory responses indicated by no release of IL-1β when stimulated with LPS and ATP, reduced IL-6 production, loss of L-selectin shedding, and significantly reduced susceptibility to monoclonal anti-collagen-induced arthritis. P2rx7 is also involved in regulating normal bone structure. Long bones from these mice have reduced periosteal bone formation and circumference, as well as diminished total and cortical bone content. This strain may be useful for researching the IL-1α and IL-1β processing pathways, proinflammatory responses, autoimmune diseases, and the regulation of bone formation and resorption.
B6.129S4-Grin1tm2Stl/J (005246)
These mice possess loxP sites flanking approximately 12kb of sequence of the targeted glutamate receptor, ionotropic, NMDA1 (zeta 1) (Grin1) gene. The floxed sequence encodes the entire transmembrane domain and C-terminal region of the protein. Homozygotes are viable, fertile, and look and behave normally. These receptors require input from both presynaptic and postsynaptic reactions, and, when active, allow calcium influx, which in turn stimulates biochemical pathways that influence synaptic activity. Grin1 function in the CA1 region of the hippocampus has been associated with spatial learning. When mated with a Cre recombinase-expressing strain, this strain is useful for generating tissue-specific mutants of the floxed allele.
