Newly Available JAX® Mice Strains
JAX® NOTES Issue 508, Winter 2008
Below is a partial list of newly available JAX® Mice strains. For a complete list, see Newly Available Strains.
For ordering information, please contact Customer Service at orderquest@jax.org, 800-422-6423, or 207-288-5845.
Please see our Web site.
Diabetes Research
FVB.BKS(D)-Leprdb/ChuaJ 006654
The phenotype of this FVB strain congenic for the spontaneous diabetes (db) mutation of the leptin receptor (Lepr) gene varies from that of other strain backgrounds with the same mutation. Whereas the original C57BLKS/J-Leprdb strain is hyperglycemic due to hypoinsulinemia and loss of beta-cell mass, this strain appears to be hyperglycemic because of severe insulin resistance (accompanied by continual increases in insulin secretory capacity from beta-cell mass expansion). Homozygous, obese FVB-Leprdb mice show evidence of mesangial matrix expansion, a hallmark of diabetic nephropathy. This strain and others with the Leprdb mutation may be used to research diabetes, including the genetic control of beta-cell responses to hyperglycemia and insulin resistance and sensitivity.
Immunology Research
NOD.129S2(B6)-Airetm1.1Doi/DoiJ 006360
The autoimmune regulator (Aire) gene partly controls ectopic gene expression involved with tolerance induction. In humans, it is involved with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. In this strain, exon 2 and portions of the flanking introns of the Aire gene have been deleted by lox/cre mediated homologous recombination. Analysis of the mutated Aire transcript reveals a frameshift that precludes translation past exon 1. Mice of this strain are normoglycemic, but they lose weight when between 5 and 15 weeks old, and 79% die or must be discarded. They develop lesions with generalized pneumonitis, severe exocrine pancreatitis, lymphocytic infiltration in the liver, salivary glands, stomach, and reproductive system, and circulating autoantibodies against the ovaries, stomach, retina, and exocrine pancreas. This strain may be used to research Aire function in autoimmunity and tolerance induction.
C.Cg-Foxp3tm2Tch/J 006769
Homozygotes for this targeted mutation of the forkhead box P3 (Foxp3) gene are viable, fertile, and develop normal T and B cells. This strain co-expresses enhanced green fluorescent protein (EGFP) and the Foxp3 gene under the control of the endogenous promoter on the X chromosome. EGFP expression accurately identifies the Foxp3+ T cell population (more than 97% of Foxp3+ T cells are EGFP+), and Foxp3 mRNA expression strictly segregates with EGFP+ T cells. Due to X-inactivation in females, the number of EGFP+CD4+ T cells found in the peripheral blood of heterozygous females is approximately half of that in hemizygous males. Following anti-CD3 and anti-CD28 mAb stimulation, CD4+EGFP+ regulatory T cells suppress effector cell proliferation normally. Some EGFP expression occurs in a small population of CD8+ thymocytes. This strain may be used to research regulatory T cell proliferation, localization, and antigen independence during the primary immune response.
C57BL/6-Tg(Tcra2D2,Tcrb2D2)1Kuch/J 006912
This "2D2 TCR" (or MOG 35-55 specific TCR) strain is transgenic for the mouse T-cell receptor alpha and beta chain (Tcra and Tcrb) transgenes. Hemizygotes are viable and fertile. Myelin oligodendrocyte glycoprotein (MOG)-specific transgenic T cells are neither deleted nor tolerized and are functionally competent. The majority of T cells express high and intermediate levels of T cell receptor (TCR), indicating that transgenic T cells are efficiently and positively selected. The majority of CD4+ splenocytes express the Tcra and Tcrb transgenes (as defined by Valpha3.2 and Vbeta11 expression). Cultured splenocytes respond to whole MOG and MOG 35-55 peptide, but not to OVA control peptides. Whereas 4% of 2.5- to 5-month old 2D2 TCR mice develop spontaneous experimental autoimmune encephalomyelitis (EAE), 40% of them develop spontaneous isolated optic neuritis with neither clinical nor histological evidence of EAE within the first year of life. Although standard inducible EAE protocols lead to typical EAE, suboptimal doses of injected MOG are sufficient to trigger optic neuritis but spare the rest of the central nervous system from EAE. This strain may be used to study the MOG-specific self-reactive repertoire and optic neuritis.
Infectious Disease Research
B6.129S4-Timp1tm1Pds/J 006243
Homozygous females and hemizygous males for this X-linked targeted mutation of the tissue inhibitor of metalloproteinase 1 (Timp1) gene are viable and fertile. Northern blot analyses of lung tissue reveal no Timp1 transcript. Homozygotes exhibit the following phenotypes: increased resistance to corneal and pulmonary infection with P. aeruginosa; altered immune, hematopoietic, and vascular permeability in bleomycin-induced lung injury trials; and more aneurisms than in wild-type thoracic aortic aneurysm (TAA) models. This strain may be used to research cornea and pulmonary infection, pulmonary injury and aneurysm, and P. aeruginosa resistance with unresolved antibiotic-resistant pulmonary infections similar to those observed in cystic fibrosis patients.
Neurobiology Research
B6.129P2-Mecp2tm2Bird/J 006849
This strain possesses a loxP-flanked STOP cassette in intron 2 of the methyl CpG binding protein 2 (Mecp2) gene on the
X chromosome. Western blot and hybridization analyses confirm the absence of wild-type MECP2 protein. Hemizygous males do not breed and develop Rett syndrome symptoms (reduced mobility, hindlimb clasping) when around 6 weeks old and die when around 11 weeks old. Heterozygous females are fertile until they develop Rett syndrome characteristics when 4-12 months old. The Rett syndrome-like phenotype is similar to that in Mecp2 knockout strain B6.129P2(C)-Mecp2tm1.1Bird/J (003890). Cre recombinase-mediated removal of the floxed-STOP cassette restores Mecp2 transcription, normalizes MECP2 protein activity, and reverses the Rett syndrome-like neurological defects. This strain may be bred to one expressing tamoxifen-inducible cre recombinase in most tissues (see B6.Cg-Tg(cre/Esr1)5Amc/J, 004862) to research Rett syndrome.
Research Tools, Conditional Mutants
B6.Cg-Tg(ACTFLPe)9205Dym/J 005703
This transgenic strain expresses a variant of the Saccharomyces cerevisiae Flp1 recombinase gene under the direction of the human actin beta (ACTB) promoter. The recombinase variant exhibits enhanced thermostability: recombination activity is four-fold and ten-fold times that of wild-type recombinase at 37oC and 40oC respectively. Hemizygotes are viable, fertile, and look and behave normally. Recombinase activity occurs in many tissues (spinal cord, heart, gonad, adrenal) as early as embryonic day 10.5. This deleter strain is a suitable alternative to, and complement with, the Cre-loxP system for in vivo genetic engineering.
B6;129-Baxtm2Sjk Bak1tm1Thsn/J 006329
Homozygotes for targeted mutations of both the Bcl2-associated X protein (Bax) and the BCL2-antagonist/killer 1 (Bak1) genes are viable, fertile, and have no reported abnormalities. Splenic and thymic tissues express no Bak1 protein. When this strain is bred to a Cre recombinase-expressing strain, offspring are produced in which Bax exons 2-4 are deleted in the tissues directed by the cre promoter. The conditional deletion along with the Bak1 null allele make this strain useful for researching apoptosis regulation, tissue homeostasis, and development.
FVB-Tg(Ckmm-cre)5Khn/J 006405
This transgenic strain expresses cre recombinase under the control of the mouse muscle creatine kinase (MCK or Ckm) promoter. Hemizygotes are viable, fertile, and look and behave normally. Cre activity occurs in skeletal and cardiac muscle. When this strain is bred with one containing a loxP-flanked sequence of interest, offspring are produced in which Cre-mediated recombination deletes the flanked genome in skeletal and cardiac muscle. This cre-lox strain may be used in cardiovascular and diabetes research.
B6.FVB(129S4)-Tg(Ckmm-cre)5Khn/J 006475
This transgenic strain, congenic on the C57BL/6 background, expresses cre recombinase under the control of the muscle creatine kinase (MCK or Ckm) promoter. Hemizygotes are viable, fertile, and look and behave normally. Cre activity is observed in skeletal and cardiac muscle. When this strain is bred with one containing a loxP-flanked sequence of interest, offspring are produced in which Cre-mediated recombination deletes the sequence in skeletal and cardiac muscle.
Research Tools, Fluorescent Proteins
STOCK Gt(ROSA)26Sortm1(DTA)Jpmb/J 006331
Homozygotes for this targeted mutation of the gene trap ROSA 26 (Gt(ROSA)26Sor) gene are viable and look and behave normally. The donating investigator reports that some males are subfertile. This strain expresses enhanced green fluorescent protein (EGFP) ubiquitously, but transcription of the diphtheria toxin A (DTA) subunit is prevented by a strong transcriptional stop sequence. When this strain is bred to one with a Cre recombinase gene under the control of a promoter of interest, offspring are produced in which the loxP-flanked EGFP and stop sequence are removed, the DTA subunit is expressed, and cre-expressing cells are ablated. This strain may be used alone as a fluorescent reporter, along with a cre-expressing strain to conditionally delete specific groups of cells, or to research toxicology and protein synthesis.
STOCK Tg(Gad1/EGFP)98Agmo/J 006340
This transgenic strain expresses enhanced green fluorescent protein (EGFP) under the direction of the mouse glutamic acid decarboxylase 1 (Gad1) promoter. Hemizygotes are viable, fertile, and look and behave normally. In the neocortex, EGFP is expressed mostly in layers 5B and 6, and to a lesser extent in layers 2/3. EGFP is also expressed in area CA1 of the hippocampus, mainly in large interneurons in the oriens-alveus layers. Fluorescence occurs in infragranular, calbindin immunoreactive interneurons with axonal arborizations in layer 1 of the neocortex and at low levels in small cells with glial morphology. Mice younger than 2 weeks old have an increased number of EGFP-labeled neurons in the supragranular layers. These young mice also express EGFP in some cells with pyramidal morphology. The location, neurochemical markers, axonal morphologies, and electrophysiological characteristics of the fluorescently labeled neuron populations in this founder line are distinct from those in the subset of somatostatin-containing (SOM+) interneurons in founder line 94 (STOCK Tg(Gad1/EGFP)94Agmo/J, 006334), and from those in mice expressing Tg(GadGFP)45704Swn (FVB-Tg(GadGFP)45704Swn/J, 003718). This strain may be used to research populations of inhibitory interneurons in the hippocampus and neocortex.
