FTO (human) (IntraCellular) ELISA Kit

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					P R O D U C T F LY E R                                                                                           International Edition




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                         FTO

                         FTO – A Gene Contributing to Human Obesity
                         The Fto gene was first cloned after identification     conserved and three of them are homologous to E.
                         of a Fused toe (Ft) mutant mouse, whose pheno-         coli AlkB and its eukaryotic homologs, members of
                         type arised from a 1.6mb deletion of six genes,        the ABH (AlkB homolog) family [7]. AlkB is a mem-
                         including Fto [1, 2]. FTO is a very large gene, also   ber of the 2OG-FE(II) oxygenase superfamiliy that
                         known as fat mass and obesity associated gene. In      oxidatively demethylates DNA [7, 8]. 2OG-FE(II) ox-
                         human, it is located on chromosome 16, consist-        ygenases are involved in diverse processes, such
                         ing of 9 exons and spanning more than 400kb [3].       as DNA repair, fatty acid metabolism and post-
                         FTO mRNA is widely expressed in human tissues. In      translational modifications. In vitro studies have
                         the mice brain, Fto is highly expressed in hypoth-     shown, that FTO can catalyze the demethylation
                         alamic nuclei that control eating behavior [4, 5].     of 3-methyluracil in single-stranded RNA with a
                         It was believed, that only vertebrates are carriers    slightly higher efficiency over that of 3-methyl-
                         of the FTO/Fto gene. To date, also FTO homologs        thymine in double- or single-stranded DNA [9].
                         in evolutionary diverse marine eukaryotic algae        However, it remains to be shown how an altered
                         were identified. The biological roles of these ma-     demethylase activity is associated with obesity.
                         rine algal FTO homologs are still unknown [6].
                         Four regions in the FTO gene are particularly well                                   CONTINUED ON NEXT PAGE




                           FTO (human) (IntraCellular) ELISA Kit
                            • Excellent Quality
                            • High Sensitivity
                            • Batch-to-Batch Reproducibility


                            For Details see Backcover




                            Connecting Immunology to Metabolism™
FTO                                                                                                                                         International Edition


      Based on twin studies, it was known for years, that the develop-      LITERATURE REFERENCES:
      ment of obesity in response to a particular environment under-        [1] Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse muta-
      lies some genetic factors [10]. Some specific FTO gene variations     tion: T. Peters, et al.; Mamm. Genome 10, 983 (1999)
      were shown to correlate directly with obesity and even more,          [2] The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including
                                                                            the entire Iroquois B gene cluster: T. Peters et al.; Mamm. Genome 13, 186 (2002)
      with type-II diabetes (T2D). The first intron of the FTO gene con-
                                                                            [3] Regulation of Fto/Ftm gene expression in mice and humans: G. Stratigopoulos,
      tains several SNPs (single nucleotide polymorphisms). 10 differ-      et al.; Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, 1185 (2008)
      ent SNPs correlating with an increased obesity risk have been         [4] A Common Variant in the FTO Gene Is Associated with Body Mass Index and
      identified within this intron. So far, only some SNPs were fur-       Predisposes to Childhood and Adult Obesity: T.M. Frayling, et al.; Science 316, 889
      ther investigated [4]. The SNP rs9939609 A-allele for example in-     (2007)
      creases the risk of obesity and T2D. Gathered data show that the      [5] Variation in FTO contributes to childhood obesity and severe adult obesity: C.
                                                                            Dina, et al.; Nat. Genet. 39, 724 (2007)
      effects on obesity are allelic dose dependent [4, 11]. Within the
      FTO gene, rs9930506 showed the strongest association with BMI         [6] The FTO Gene, Implicated in Human Obesity, Is Found only in Vertebrates and
                                                                            Marine Algae: S. Robbens, et al.; J. Mol. Evol. 66, 80 (2008)
      (Body Mass Index), hip circumference, and weight [12]. These
                                                                            [7] The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic
      findings were reproduced for many Caucasian populations. Ini-         Acid Demethylase: T. Gerken, et al.; Science 318, 1469 (2007)
      tial studies in Asians and lately also with an African population     [8] The FTO (fat mass and obesity associated) gene codes for a novel member of
      showed no association between FTO variants and the BMI or             the non-heme dioxygenase superfamily: L. Sanchez-Pulido, et al.; BMC Biochem.
      obesity [13-16]. However, other studies with Chinese, Koreans,        8, 23 (2007)
      Malay Japanese, European Americans and Hispanic Americans             [9] Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-strand-
                                                                            ed DNA and RNA by mouse and human FTO: G. Jia, et al.; FEBS Letters 582, 3313
      supported the association between FTO variants and obesity in         (2008)
      such populations [12,15, 17-21]. Even though there is an asso-
                                                                            [10] Genetic and Environmental Factors in Relative Body Weight and Human Adi-
      ciation between FTO variants and the susceptibility to obesity,       posity: H.H.M. Maes, et al.; Behav. Genet. 27, 325 (1997)
      this can be overcome in part by physical activity [22].               [11] Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus
      A recent publication with mice showed that the inactivation of        in the French MONICA Study: V. Legry, et al.; Metabolism 58, 971 (2009)
      the Fto gene protects from obesity. The generated Fto-null mice       [12] Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are As-
                                                                            sociated with Obesity-Related Traits: A. Scuteri, et al.; PLoS Genet. 3, 1200 (2007)
      lead to postnatal growth retardation and a significant reduc-
                                                                            [13] Variants in the Fat Mass-and Obesity-Associated (FTO) Gene Are Not Associated
      tion in adipose tissue and lean body mass [23]. However, the          With Obesity in a Chinese Han Population: H. Li, et al.; Diabetes 57, 264 (2008)
      induction of hypothalamus development seems to be normal.             [14] Variations in the HHEX gene are associated with increased risk of type 2 diabetes
      The leanness of Fto-deficient mice results from an increased          in the Japanese population: M. Horikoshi, et al.; Diabetologia 50, 2461 (2007)
      energy expenditure in the presence of reduced spontaneous             [15] Association between the FTO rs9939609 polymorphism and the metabolic syn-
      locomotor activity, with a relative hyperphagia. Interestingly,       drome in a non-Caucasian multi-ethnic sample: S.A. Al-Attar, et al.; Cardiovasc. Dia-
      human carriers of the FTO gene risk allele seem to develop obes-      betol. 7, 5 (2008)
      ity as a consequence of hyperphagia, without altered energy           [16] FTO polymorphism in oceanic populations: J. Ohashi, et al.; J. Hum. Genet. 52,
                                                                            1031 (2007)
      expenditure as observed in mice [23]. The results are so far the
                                                                            [17] Replication of Genetic Effects of FTO Polymorphisms on BMI in a Korean Popu-
      first direct evidence of the energy homeostasis function of Fto       lation: S.W. Cha, et al.; Obesity 16, 2187 (2008)
      and by that, maybe also of human FTO.                                 [18] Common Variation in the Fat Mass and Obesity-Associated (FTO) Gene Con-
      A theory proposes that the human FTO gene regulates the near-         fers Risk of Obesity and Modulates BMI in the Chinese Population: Y.C. Chang, et
      by gene KIAA1005 [4]. KIAA1005 is also ubiquitously expressed         al.; Diabetes 57, 2245 (2008)
      and the similar expression profile between these two genes may        [19] FTO Variants Are Associated With Obesity in the Chinese and Malay Populations
                                                                            in Singapore: J.T. Tan, et al.; Diabetes 57, 2851 (2008)
      be an indication for a joint transcriptional regulation. The SNP
                                                                            [20] Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 With
      rs9939609 is highly correlated with 45 additional SNPs within         Susceptibility to Type 2 Diabetes in a Japanese Population: S. Omori, et al.; Diabe-
      a 47kb region of the FTO gene. This region consists of the first      tes 57, 791 (2008)
      two introns as well as the second exon of the FTO gene. The           [21] Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B,
      47kb region might be a key player in altering the expression of       IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians: M.C. Ng, et al.; Dia-
                                                                            betes 57, 2226 (2008)
      FTO, KIAA1005, or more distant genes [4]. Though, a study has
                                                                            [22] Physical activity attenuates the body mass index-increasing influence of genetic
      shown that the FTO expression in human adipose tissue and             variation in the FTO gene: K.S. Vimaleswaran, et al.; Am. J. Clin. Nutr. 90, 425 (2009)
      skeletal muscle is low and not influenced by obesity associ-
                                                                            [23] Inactivation of the Fto gene protects from obesity: J. Fischer, et al.; Nature 458,
      ated FTO variants [24]. If this is also true for hypothalamic FTO     894 (2009)
      expression needs to be investigated. Today it is known, that          [24] Regulation and function of FTO mRNA expression in human skeletal muscle
      the mice Fto mRNA levels in the hypothalamic nuclei are up-           and subcutaneous adipose tissue: L.G. Grunnet, et al.; Diabetes Epub ahead of print,
      regulated by feeding and down-regulated by food deprivation.          (2009)
      The effect of starvation in rats is the opposite to that observed     [25] The Obesity Gene, FTO, Is of Ancient Origin, Up-Regulated during Food Depri-
                                                                            vation and Expressed in Neurons of Feeding-Related Nuclei of the Brain: R. Fredriks-
      in mice [7, 25]. However, the underlying mechanism how the            son, et al.; Endocrinology 149, 2062 (2008)
      FTO mRNA concentration is regulated by FTO variants and food
      intake needs still to be studied.
                                                                              SELECTED REVIEW ARTICLES
                                                                              • Gender in Childhood Obesity: Family Enivronment, Hormones, and Genes:
                                                                                A.B. Wisniewski, et al.; Gend. Med. 6, 76 (2009)
                                                                              • Nutrition and its contribution to obesity and diabetes: a life-course approach
                                                                                to disease prevention?: M.E. Symonds; Proc. Nutr. Soc. 68, 71 (2009)
                                                                              • Is Obesity Our Genetic Legacy?: A.I.F. Blakemore & P. Froguel; J. Clin. Endocri-
                                                                                nol. Metab. 93, 51 (2008)




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                                                                                                                                               APOPTOSISTO
International Edition




                                                                                                                                                       F
                            SNP rs9939609 is associated with
 L AT E S T I N S I G H T

                            C-reactive Protein Levels                                                   Leading in
                            E. Fisher, et al. discovered an association between FTO vari-



                                                                                                        Obesity
                            ants and an increased C-reactive Protein (CRP) level. Their data
                            indicate that FTO variation might contribute to a variation in
                            plasma CRP levels, without showing obesity indices. Further-
                            more they hypothesize that FTO variants partly contribute to
                            an increased cardiovascular risk.
                            LIT: Association of the FTO rs9939609 Single Nucleotide Polymorphism
                            With C-reactive Protein Levels: E. Fisher, et al.; Obesity 17, 330 (2009)

                                                                                                        Research
                            Severe growth retardation and                                                    PURE PROTEINS
 L AT E S T I N S I G H T




                            multiple malformations by loss-of-                                                    SPECIFIC ANTIBODIES
                            function mutation in the FTO gene                                                 SENSITIVE ELISA KITS
                            FTO protein is homolog to the E. coli AlkB 2OG-FE(II) oxyge-
                            nase superfamiliy. Inactivating the FTO enzymatic activity
                            by a R316Q mutation leads to an autosomal-recessive lethal
                            syndrome. Cultured skin from affected subjects showed im-
                            paired proliferation and accelerated senescence. S. Boissel, et
                            al. suggested that FTO is essential for normal development
                            of the central nervous and cardiovascular system. Mutations
                                                                                                        Panel of Adipokines
                            in the human FTO gene result in a severe polymalformation
                            syndrome.
                            LIT: Loss-of-function mutation in the dioxygenase-encoding FTO gene
                                                                                                        Angiopoietin-like Proteins
                            causes severe growth retardation and multiple malformations: S. Bois-
                            sel, et al.; Am. J. Hum. Genet. 85, 106 (2009)
                                                                                                        Nampt
                                                                                                        Omentin
                            A Novel Locus for Obesity: NRXN3
 L AT E S T I N S I G H T




                                                                                                        Sirtuins
                            In the NRXN3 (neurexin 3) gene, the SNP (single nucleotide
                            polymorphism) rs10146997 is associated with an altered waist
                            circumference, the risk for obesity and BMI (Body Mass Index).
                            Beside FTO and MC4R, NRXN3 might be another important
                                                                                                        Vaspin
                            gene associated to obesity. Many of the neuronal pathways
                            in the sub-cortical regions of the brain in which NRXN3 is ex-
                            pressed are involved with learning and reward training. The
                            NRXN3 gene is also associated with substance abuse.
                            LIT: NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide          Connecting Immunology to Metabolism™
                            Association Study from the CHARGE Consortium: N.L. Heard-Costa, et
                            al.; PLoS Genet. 5, e1000539 (2009)




For updated prices and additional information visit www.axxora.com or call your local distributor.                                               3
Products
Proteins                                                                                              Antibodies
            FTO (human) (rec.) (His)                                                                  anti-FTO (human), mAb (FT86-4)
AG-40A-0112-C010                                                                            10 μg     AG-20A-0064-C050                                                                       50 μg
AG-40A-0112-C050                                                                            50 μg     AG-20A-0064-C100                                                                      100 μg
Expressed in E. coli. The mature peptide of human FTO (aa 2-505)                                      CLONE: FT86-4. ISOTYPE: Mouse IgG1. IMMUNOGEN: Recombinant human
is fused at the N-terminus to a His-tag. PURITY: ≥90% (SDS-PAGE).                                     FTO. SPECIFICITY: Recognizes human FTO. APPLICATION: ELISA, WB.
ENDOTOXIN CONTENT: <1EU/μg protein (LAL-test).
                                                                                                                                     FIGURE: Western blot analysis of human FTO using anti-FTO (hu-
                    FIGURE: SDS-PAGE of FTO (human) (rec.) (His) (Prod. No. AG-40A-0112).                                            man), mAb (FT86-4) (Prod. No. AG-20A-0064) at 1:2’000 dilution.
                                                                                                                                     1. FTO (human) (rec.) (His) (Prod. No. AG-40A-0112)
                                                                                                                                     2. Recombinant mouse Vaspin (His-tagged) (negative control)




                                                                                                                  anti-FTO, mAb (FT403-2)
            FTO (mouse) (rec.) (His)                                                                  AG-20A-0075-C050                                                                       50 μg
AG-40A-0127-C010                                                                            10 μg     AG-20A-0075-C100                                                                      100 μg
AG-40A-0127-C050                                                                            50 μg     CLONE: FT403-2. ISOTYPE: Mouse IgG2. IMMUNOGEN: Recombinant hu-
Expressed in E. coli. The mature peptide of mouse FTO (aa 2-502)                                      man FTO. SPECIFICITY: Recognizes human and mouse FTO. APPLICA-
is fused at the N-terminus to a His-tag. PURITY: ≥90% (SDS-PAGE).                                     TION: ELISA, WB.
ENDOTOXIN CONTENT: <1EU/μg protein (LAL-test).
                                                                                                                                     FIGURE: Western blot analysis of FTO using anti-FTO (human), mAb
                    FIGURE: SDS-PAGE of FTO (mouse) (rec.) (His) (Prod. No. AG-40A-0127).                                            (FT403-2) (Prod. No. AG-20A-0075) at dilution 1:2’000.
                                                                                                                                     1. FTO (human) (rec.) (His) (Prod. No. AG-40A-0112)
                                                                                                                                     2. FTO (mouse) (rec.) (His) (Prod. No. AG-40A-0127)
                                                                                                                                     3. HEK293 T cell lysate
                                                                                                                                     4. Recombinant human Sirtuin 2 (His-tagged) (negative control)




                                                                                                      anti-FTO (human), pAb
  ELISA Kit                                                                                           AG-25A-0084-C100                                                                      100 μg
                                                                                                      From rabbit. IMMUNOGEN: Recombinant human FTO. SPECIFICITY: Rec-
               FTO (human) (IntraCellular) ELISA Kit                                                  ognizes human FTO. APPLICATION: ELISA, WB.
  AG-45A-0025EK-KI01                                                           1 x 96 wells
  AG-45A-0025TP-KI01             Twin Plex                                     2 x 96 wells           anti-FTO (mouse), pAb
  For the quantitative determination of intracellular FTO in hu-                                      AG-25A-0089-C100                                                                      100 μg
  man cell lysates. SENSITIVITY: 50pg/ml (range 0 to 10ng/ml).                                        From rabbit. IMMUNOGEN: Recombinant mouse FTO. SPECIFICITY: Rec-
                                                                                                      ognizes mouse FTO. Weakly cross-reacts with human FTO. APPLICA-
                                                                                                      TION: ELISA, WB.




Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections);
WB = Western blot; BP = Blocking Peptide




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