Search Criteria: Research Area is "Research Tools: Dermatology Research"
| Stock Number |
Strain Name Strain Description |
Standard Supply |
| 013787 | B6.129S1-Abcc6tm1Jfk/J | Repository- Live |
| Mice that are homozygous for this targeted mutation develop patchy, progressive mineralization of the dermis, kidneys, eyes, arteries, heart and subcutaneous tissues, mimicking the human disease symptoms of pseudoxanthoma elasticum. Mineralization of connective tissue capsule surrounding vibrissae is detectable at 5 weeks of age. Mineralization is associated with collagen fibrils and elastic fibers. Oxidative stress, as indicated by lipid peroxidation and protein oxidation, is higher in liver tissue and serum of mutant mice when compared to wildtype controls. Antioxidant diet reduces the oxidative stress levels in knock out mice, but does not prevent ectopic mineralization. The severity of mineralization can be altered by mineral intake as a diet with elevated magnesium levels prevents pathological connective tissue mineralization in mutants. Serum matrix gla protein (MGP) levels are reduced in homozygotes and the protein is under-carboxylated with diminished activity. Fetuin-A ..... For more information please see the full phenotype on the strain data sheet | ||
| 012564 | B6.129S5-Dhcr24tm1Fein/SbpaJ | Repository- Live |
| Homozygous mice on the C57BL/6 genetic background die within the first postnatal day with features of lethal restrictive dermopathy; including taut, wrinkle-free, shiny skin, severe defects in epidermal maturation/epidermal barrier function (impaired epidermal development), and increased presence of hyperproliferative immature keratinocytes (defective keratinocyte differentiation). The increased transepidermal water loss/increased epidermal water content is associated with increased aquaporin-3 (AQP3) expression throughout the epidermis. Mice heterozygous for this allele are viable and fertile, with no overt phenotype. As the Dhcr24 protein functions to catalyze the last step of cholesterol biosynthesis (the conversion of desmosterol to cholesterol), homozygous disruption of this locus results in desmosterolosis: almost no cholesterol in plasma and tissues with ~99% of total sterols in the form of desmosterol. lacZ expression from the mutant allele is not characterized.
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| 008712 | B6.129X1-Twist2tm1.1(cre)Dor/J | Repository- Live |
| Dermo1-cre (Twist2-cre) mutant mice harbor a Cre recombinase "knock-in" allele that also abolishes endogenous Twist2 gene function. Heterozygotes are viable and fertile, while homozygotes (twist-2-/-) die a few days after birth. Under control of the upstream promoter/enhancer elements, cre expression is observed in a pattern consistent with the wildtype gene; Cre recombinase activity is reported in mesoderm as early as embryonic day 9.5, in mesodermal tissues such as branchial arches and somites, and in condensed mesenchyme-derived chondrocytes and osteoblasts. When heterozygotes are bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequences in Dermo1-expressing tissues of the offspring. Homozygous mice exhibit elevated expression of proinflammatory cytokines resulting in perinatal death from cachexia (wasting), as well as progressive growth retardation, impaired movement, th ..... For more information please see the full phenotype on the strain data sheet | ||
| 005244 | B6.Cg-Tg(Krt1-15-EGFP)2Cot/J | Repository- Live |
| Mice hemizygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These transgenic mice express Enhanced Green Fluorescent Protein (EGFP) under the direction of the mouse keratin complex 1, acidic, gene 15 promoter. The high levels of specific transgene expression observed in 'bulge cells' (hair follicle stem cells) allow these cells to be isolated with FACS techniques. This mutant mouse strain may be useful in studies of epithelial stem cells. | ||
| 012328 | B6.Cg-Tg(Tyr-cre/ERT2)13Bos/J | Repository- Live |
| Homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Cre-ERT2 fusion gene activity can be induced following tamoxifen or 4-hydroxytamoxifen administration. When Tyr::CreERT2 mice are bred with mice containing loxP-flanked sequences, inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Tyr-expressing cells of the offspring. The donating investigator reports that Cre recombinase activity is observed in embryonic melanoblasts, follicular bulb melanocytes, dermal dendritic melanocytes, epidermal melanocytes of tail skin and ocular chorid cells. Recombinase expression was not observed in the other major tissues/organs tested. This mutant mouse strain may be useful in studies of melanocyte development, melanocyte stem cell function and melanomas. | ||
| 005440 | C.129S4-Ccr3tm1Cge/J | Repository- Live |
| Mice homozygous for this CCR3 (chemokine (C-C motif) receptor 3) targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by RNA protection assay analysis of thymus, spleen and lung tissues. Mice homozygous for the mutation have impaired trafficking of eosinophils. A 7-fold decrease in the number of eosinophils in the small intestine and a 6-fold increase in the spleen is observed. Aerosol allergen challenge does not cause the expected infiltration of eosinophils to the lung tissue and airway lumens (50-70% reduction), although abundant eosinophils are found in the airway blood vessels. Concurrent increases in eosinophils in the spleen and intraepithelial mast cells in the spleen occur after allergen challenge. Homozygotes exhibit increased bronchoconstriction with allergen-induced airway hyperresponsiveness. There is no increase in eosinophils or eosinophil product major basic protein (M ..... For more information please see the full phenotype on the strain data sheet | ||
| 004623 | STOCK Tg(Fos-lacZ)34Efu/J | Repository- Live |
| These TOPGAL transgenic mice are a reporter strain that express Beta-galactosidase in the presence of the lymphoid enhancer binding factor 1/transcription factor 3 (LEF/TCF) mediated signaling pathway and activated Beta-catenin. The transgene contains the lacZ gene under the control of a regulatory sequence consisting of three consensus LEF/TCF-binding motifs upstream of a minimal c-fos promoter. Transgenic mice display TOPGAL activity (Beta-galactosidase activity) during early embryonic development in a subset of pluripotent embryonic basal cells of the epithelium and dermis of developing hair follicles, but not during the next stage of hair follicle development; formation of hair germs. TOPGAL transgene activity reappears in hair follicles at E16.5 and TOPGAL expression is strongly upregulated in the postnatal hair shaft precursor cells in both whisker and body hair anagen follicles (active periods of hair growth). TOPGAL expression ceases during catagen (regression and ..... For more information please see the full phenotype on the strain data sheet | ||
| 005107 | STOCK Tg(KRT14-cre/ERT)20Efu/J | Repository- Live |
| These transgenic mice have a tamoxifen inducible Cre-mediated recombination system driven by the human keratin 14 (KRT14) promoter. The transgene insert contains a fusion product involving Cre recombinase and a mutant form of the mouse estrogen receptor ligand binding domain. The mutant mouse estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen (tamoxifen). Restricted to the cytoplasm, the cre/Esr1 protein can only gain access to the nuclear compartment after exposure to tamoxifen. When crossed with a strain containing a loxP site flanked sequence of interest, the offspring are useful for generating tamoxifen-induced, Cre-mediated targeted keratinocyte-specific deletions. Oral tamoxifen administration induces Cre recombination in toe, back skin and tongue. Topically administered tamoxifen induces Cre-mediated recombination in a specific localized area of the skin, occuring in 50 to 60% of the ..... For more information please see the full phenotype on the strain data sheet | ||
| 006403 | 129S.B6-Tg(KRT14-Esr1/HRAS)1Pkha/J | Cryopreserved - Ready for recovery |
| Mice hemizygous for this "K14-ER:Ras" transgene are viable and fertile, with expression of the ER:Ras fusion protein (constitutively active G12V mutant form of the catalytic domain of human H-ras (H-rasV12) fused at its amino terminal with the G525R mutant murine estrogen receptor ligand binding domain (ERTM)) directed to epidermis by the human keratin 14 promoter. Because of the ERTM region of the fusion protein, ER:Ras is restricted to the cytoplasm and the biochemical activity of the ER:Ras fusion gene can be induced following tamoxifen administration. For example, prolonged (4 weeks) induction of human H-RasG12V activity promotes the undifferentiated, proliferative phenotypic characteristics observed in epidermal cancer; including hyperplasia, increased mitotic index, decreased expression of differentiation markers and increased expression of beta-1 and beta-4 integrin subunits. H-RasG12V-induced skin abnormalities were entirely reversed ..... For more information please see the full phenotype on the strain data sheet | ||
| 006661 | 129S.B6-Tg(KRT14-RAF1/ESR1)1Pkha/J | Cryopreserved - Ready for recovery |
| Mice hemizygous for this "K14-Raf:ER" transgene are viable and fertile, with expression of the Raf:ER fusion protein (a constitutively active Y340D/Y341D mutant form of the catalytic domain of human Raf-1 (Raf-1[DD]) fused at its carboxy terminal with the G525R mutant human estrogen receptor ligand binding domain (ERTM)) directed to epidermis by the human keratin 14 promoter. Because of the ERTM region of the fusion protein, Raf:ER is restricted to the cytoplasm and the biochemical activity of the Raf:ER fusion gene can be induced following tamoxifen administration. For example, prolonged (4 weeks) induction of human Raf-1[DD] activity promotes the undifferentiated, proliferative phenotypic characteristics observed in epidermal cancer; including hyperplasia, increased mitotic index, decreased expression of differentiation markers and increased expression of beta-1 and beta-4 integrin subunits. Raf-1[DD]-induced skin abnormalities are entirely reversed within one m ..... For more information please see the full phenotype on the strain data sheet | ||
| 003509 | B6.129-Blmhtm1Geh/J | Cryopreserved - Ready for recovery |
| Bleomycin (BLM) is a clinically used glycopeptide anticancer agent. It is deaminated in vitro by BLMH. Blmh null mice have decreased viability and fertitility. Only about 65% of the expected number survive the neonatal period. Mice lacking Blmh exhibit variably penetrant tail dermatitis that resembles rodent ringtail. This resembles skin lesions in humans with pellagra, necrolytic migratory erythema, and acrodermatitis enteropathica. Null mice also are more sensitive to acute BLM lethality and develop pulmonary fibrosis following BLM treatment. | ||
| 006201 | B6.129-Scd1tm1Ntam/J | Cryopreserved - Ready for recovery |
| Homozygous mice are viable and fertile. Transcripts from the targeted gene are absent in homozygous liver, eyelid, skin, and white adipose tissues. In addition, the endogenous protein and enzyme activity are absent from homozygous liver tissue. Homozygous mice exhibit cutaneous abnormalities and narrow eye fissure with atrophic sebaceous and meibomian glands. Mutant mice also have reduced body adiposity, increased insulin sensitivity, increased basal and insulin-mediated glucose uptake, and are resistant to diet-induced weight gain. Homozygotes have altered hepatic glycerophospholipid profiles. Homozygous mice are not recommended for breeding as skin lesion severity may prohibit colony success. These mutant mice may be useful in studies of monounsaturated fatty acid synthesis, cholesterol homeostasis, skin disease, obesity, and diabetes. In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background differ ..... | ||
| 006879 | B6.129-Scd2tm1Myz/J | Cryopreserved - Ready for recovery |
| While heterozygous mice are viable and fertile, mice homozygous for this targeted allele die within 24 hours of birth. Brain tissues from homozygous mice show no expression from the targeted gene. Homozygotes exhibit neonatal lethality with 100% penetrance on this genetic background (less penetrant on 129SvEv genetic background) likely due to severe skin permeability barrier abnormalities. Null mice also have abnormal epidermal morphology and abnormal lipid homeostasis in the skin and liver. These mutant mice may be useful in studying monounsaturated fatty acid synthesis, lipid biosynthesis and metabolism, cholesterol homeostasis, and skin disease, as well as obesity and diabetes. | ||
| 006156 | B6.129-Sceltm1Hba/J | Cryopreserved - Ready for recovery |
| Homozygous mice are viable and have no overt morphological or developmental abnormalities. The donating investigator reports that fertility may be impaired in homozygous mice (limited number of litters possible). No endogenous gene expression is observed in skin or stratified squamous epithelia. These mutant mice may be useful in dermatological studies, such as cornified envelope formation, organization of the intima, as well as structural distinctions between arteries and veins, and respiratory structure and function. | ||
| 003823 | B6.129S4-Ttpatm1Far/J | Cryopreserved - Ready for recovery |
| Mice that are homozygous null for the Ttpa gene are viable, normal in size and do not display any gross physical abnormalities. The Ttpa protein product is required for the maintenance of proper alpha-tocopherol levels, the major form of vitamin E in plasma and tissues. The absence of Ttpa protein product in homozygous-null animals results in a corresponding 95% reduction in alpha-tocopherol. Low levels of alpha-tocopherol render female mice infertile, a condition that can be addressed with vitamin E supplements. Male fertility is unimpaired. These mice provide a viable model for studying vitamin E deficiency. | ||
| 006086 | B6.Cg-Tg(HBB-GH1)420King/J | Cryopreserved - Ready for recovery |
| Mice hemizygous for this transgene are viable. While males are fertile, transgenic females are unreliable breeders and mothers. Homozygotes are sterile. In both fetal and adult tissues, erythroid-specific expression of the transgene is observed. Transgenic mice have 120-150% greater mature body mass and increased bone mass. The donating investigator also reports transgenic mice have increased dermatological stiffness and toughness. Transgenic mice have a characteristic coat with few guard hairs compared to wildtype littermates. These mice may be useful in studies of bone formation and development, dermatology, and acromegaly. | ||
| 009687 | B6.Cg-Tg(KRT14-Kitl*)4XTG2Bjl/J | Cryopreserved - Ready for recovery |
| These transgenic mice express a mutant mouse Kitl (kit ligand) cDNA, TG2 or membrane SCF, under the control of the human keratin 14 (epidermolysis bullosa simplex, Dowling-Meara, Koebner), KRT14, promoter. The mutant kit ligand carries a site directed mutation that deletes the cleavage site which produces mostly membrane bound protein. These transgenic mice have epidermal melanocytes that persist into adulthood and cause grey-black pigmented skin and increased coat pigment. Shortly after birth, transgenic pups develop visibly pigmented footpads. Transgenic mice exhibit increased sensitivity to irritants. Mice that are homozygous for the targeted mutation are viable, and do not display any gross behavioral abnormalities. Homozygotes are sometimes smaller in size than wildtype controls (as reported by the Donating Investigator). This mutant mouse strain may be useful in studies of hyperpigmentation and allergic contact dermatitis. | ||
| 011080 | B6;129-Ednrbtm1.1Nat/J | Cryopreserved - Ready for recovery |
| These mice possess loxP sites flanking portions of exon 2 and intron 2 of the Ednrb (endothelin receptor type B) gene. Mice that are homozygous for this floxed allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When crossed with a Cre recombinase-expressing strain, this strain is useful in eliminating tissue-specific expression of the gene. This strain may be useful for studying the variety of functions associated with this gene ranging from coat color to cell signaling, digestive and immune phenotypes.
When crossed with a Sox2-cre transgenic strain, mice homozygous for the resulting allele lack Ednrb expression and have a phenotype identical to mice with the spotted lethal (s-l, piebald lethal) allele. | ||
| 004161 | B6;129-Fgf7tm1Efu/J | Cryopreserved - Ready for recovery |
| Mice homozygous for this targeted allele are viable, fertile and normal in size. No Fgf7 transcript is detected. By 2 months of age, the hair coat takes on a matted/greasy appearance that becomes more prominent with age. Homozygote kidneys are markedly smaller and posses structural anomalies. Morphometric analyses indicate a reduction (~30% of wildtype) in the total number of nephrons present. Kidney development appears to be effected as early as embryonic day 16.5. This mutant mouse strain represents a model that may be useful in studies related to kidney disease. | ||
| 006238 | B6;129S4-Thbs2tm1Bst/J | Cryopreserved - Ready for recovery |
| Mice homozygous for this targeted mutation are viable and fertile. Multiple analyses has confirmed the absence of protein in embryonic and adult tissue of homozygous mice. Homozygotes exhibit skin disorders (abnormal collagen fiber patterns, reduced tensile strength, increased fragility) and skin fibroblasts have attachment defects. Mice also exhibit an increase in total density/cortical thickness of the long bones, abnormally long bleeding times, and a significant increase in blood vessel density. Homozygous mice exhibit accelerated wound healing after biopsy and accelerated/increased tumor formation following chemically-induced skin carcinogenesis. Mutant mice may be useful in studies of collagen fibrillogenesis in skin and tendons, angiogenesis and vascular pathophysiology, wound healing, chemically-induced tumor progression, and as a potential model for Ehlers Danlos syndrome. In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are fre ..... | ||
| 007678 | B6;SJL-Tg(KRT14-rtTA)208Jek/J | Cryopreserved - Ready for recovery |
| Homozygous females and hemizygous males carrying this X-linked K14-rtTA transgene (K14-rtTetA(X) or rtTAX) are viable and fertile. These mice express the reverse tetracycline-controlled transactivator (rtTA) protein under the control of the human keratin 14 promoter. As the transgene is located on the X chromosome, random inactivation of the X chromosome may result in mosaic rtTA expression patterns in female mice. When mated to a second transgenic strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (TRE or tetO), expression of the target gene in the basal cells of the squamous epithelia and in the outer root sheath of the hair follicles is induced with administration of the tetracycline analog, doxycycline (dox). These K14-rtTA mice provide a Tet-On tool that allows the inducible expression of genes in skin cells. | ||
| 012645 | C.129P2(B6)-Rabgef1tm1Glli/J | Cryopreserved - Ready for recovery |
| Endogenous function of RAB guanine nucleotide exchange factor (GEF) 1 (Rabgef1 or Rabex-5) is replaced with a neomycin resistance cassette. Heterozygous mice are viable, fertile, and normal in size on the BALB/cJ background. The donating investigator states that the homozygous males are infertile due to testicular degeneration, and homozygous females develop skin diseases. All homozygous mutants are smaller in size compared to wildtype littermates. Rabgef1-/- mice exhibit elevated serum IgE, severe skin inflammation with infiltrates of lymphocytes and eosinophils, splenomegaly, lymphadenopathy, myeloid hyperplasia and high levels of the pro-allergic cytokine thymic stromal lymphopoietin (TSLP). Excessive production of TSLP may contribute to many of the phenotypes in Rabgef1-/- mice. These mice may be useful in studying pathology and development of spontaneous cutaneous inflammation, testicular degeneration, retinal degeneration, marked epidermal hyperplasia and hype ..... For more information please see the full phenotype on the strain data sheet | ||
| 002662 | C.Cg-Fechm1Pas/J | Cryopreserved - Ready for recovery |
| Homozygous mutants are recognizable by the intense yellow color of their sera, gross bilirubinemia, and, especially in albino mice, jaundice. Photosensitivity is evidenced by the appearance of inflammatory skin lesions, often becoming ulcerous, under standard mouseroom conditions (fluorescent light). Mutants do not differ from their normal littermates in body size or weight, nor are they retarded in growth. They exhibit hepatomegaly and splenomegaly, leading to enlarged abdomens after several months of age. Although mutants are not anemic at one month old, normocytic anemia develops with age. | ||
| 006125 | FVB-Tg(H2-D-Il15)3304Clgr/J | Cryopreserved - Ready for recovery |
| Mice hemizygous for this transgene are viable and fertile. The transgene was designed to optimize the overexpression of secreted, mature interleukin-15. Transgenic IL-15 expression has a similar tissue distribution as the endogenous gene, but at a significantly higher level. IL-15 protein is detectable in the serum from most mutant, but not from wildtype, mice. Mutant mice develop a progressive alopecia by as early as 5-6 weeks of age, with skin lesions appearing over time. While all transgenic mice exhibit early polyclonal/benign expansion of natural killer and memory CD8+ T lymphocytes (T/NK), two distinct phenotypes emerge over time: approximately 70% of the transgenic mice will exhibit polyclonal T/NK progression in multiple tissues, while the remaining 30% are characterized by T/NK clonal expansion in multiple tissues and acute lymphoblastic leukemia (T/NK ALL). Both T/NK phenotypes are fatal within the first year of life. Mice harboring this transgene may be useful in ..... For more information please see the full phenotype on the strain data sheet | ||
| 006822 | FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J | Cryopreserved - Ready for recovery |
| Mice hemizygous for this "K14-Mek1:ER" transgene are viable and fertile, with expression of the Mek1:ER fusion protein (a constitutively active mutant region from human mitogen activated protein kinase-kinase 1 (Mek1R4F; containing an amino-terminal deletion of aa 32-51 and the S218E/S222D substitutions) fused at its carboxy terminal with the G525R mutant murine estrogen receptor ligand binding domain (ERTM)) directed to epidermis by the human keratin 14 promoter. Because of the ERTM region of the fusion protein, Mek1:ER is restricted to the cytoplasm and the biochemical activity of the Mek1:ER fusion gene can be induced following tamoxifen administration. For example, induction of this constitutively active form of human Map2k1 (Mek1R4F) promotes the undifferentiated, proliferative phenotypic characteristics observed in epidermal neoplasia in as few as 5 days (including hyperplasia, increased levels of phosphorylated ERK1/2, increased mitot ..... For more information please see the full phenotype on the strain data sheet | ||
| 005705 | FVB-Tg(KRT14-Vegfa)3Dtm/J | Cryopreserved - Ready for recovery |
| Mice hemizygous for the transgene are viable and fertile. Transgene expression is demonstrated in the basal keratinocyte layer of the epidermis and outer root sheath keratinocytes of hair follicles. Homozygous mice spontaneously develop severe psoriasis-like lesions between 3-6 months of age, where hemizygous mice do not. Transgenic mice have increased density of tortuous cutaneous blood capillaries with elevated expression of select VEGF receptors, most prominently in neonates. Dermal mast cell localization and capillary hyperpermeability are also increased. Postcapillary venules exhibit significantly enhanced leukocyte rolling and adhesion. Transgenic expression promotes lymphangiogenesis associated not only with delayed-type hypersensitivity induced psoriasis-like skin inflammation but also with cutaneous tissue repair after wounding. Further, transgenic mice have accelerated chemically induced skin carcinogenesis with tumor associated lymphangiogenesis and angiogenesis. Elevated me ..... For more information please see the full phenotype on the strain data sheet | ||
| 016934 | B6.129P2-Lgr6tm2.1(cre/ERT2)Cle/J | Under Development - Now Accepting Orders |
| Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 6) marks a distinct stem cell population located in hair follicles. Situated directly above CD34 and keratin 15-positive stem cells in the hair follicle bulge, LGR6+ stem cells are capable of generating all cell lineages of the skin and are involved with wound repair and new hair follicle development.
Insertion of EGFP-Ires-CreERT2 into the transcriptional start site of the gene has enabled green fluorescent labeling of cells that normally express Lgr6. Prominent expression in rare cells in the brain, mammary gland, lung and skin is observed. Endogenous expression of LGR6 protein is blocked. Homozygotes are viable, healthy, and fertile.
When crossed with a Gt(ROSA)26Sor-LacZ cre reporter strain (e.g. Stock No. 003474), no leakiness of the CreERT2 is observed prior to tamoxifen induction. Single injections of tamoxifen facilitate tracking of ..... | ||
| 017519 | FVB/N-Tg(KRT5-rtTA)T2D6Sgkd/J | Under Development - Now Accepting Orders |
| These K5-rtTA transgenic mice have the bovine keratin 5 (KRT5) promoter directing expression of a nuclear localized reverse tetracycline transactivator gene (rtTA-nls). Hemizygous mice are viable and fertile. Filaments of K5 are produced by keratinocytes in the epidermis during differentiation. These assemble into networks that attach keratinocytes together and anchor the epidermis to underlying layers of skin. When mated to a second transgenic strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (TRE or tetO), expression of the target gene in the epithelial cells of the skin is induced with administration of the tetracycline analog, doxycycline (dox). These K5-rtTA mice provide a Tet-On tool that allows the inducible expression of genes in the basal layer of the epithelium.
For example, when bred to FVB/N-Tg(tetO-Kras2)12Hev/J mice (Stock No. 004375) resul ..... | ||
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