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Biomedical subjects

B Auer

Publications and source records attributed to B Auer.

At least 19 recordsLinked to original sources
PubMed2000

LST1: a gene with extensive alternative splicing and immunomodulatory function.

The gene of the leukocyte-specific transcript (LST1) is encoded within the TNF region of the human MHC. The LST1 gene is constitutively expressed in leukocytes and dendritic cells, and it is characterized by extensive alternative splicing. We identified 7 different LST1 splice variants in PBMC; thus, 14 LST1 splice variants (LST1/A-LST1/N) have been detected in various cell types. These isoforms code for transmembrane as well as soluble LST1 proteins characterized by two alternative open reading frames at their 3' end. We demonstrate the presence of the transmembrane variant LST1/C on the cell surface of the monocytic cell lines U937 and THP1. Recombinant expression of LST1/C permitted its profound inhibitory effect on lymphocyte proliferation to be observed. In contrast, the alternative transmembrane variant LST1/A, the extracellular domain of which shows no amino acid sequence homology to LST1/C exerted a weaker but similar inhibitory effect on PBMC. These data demonstrate the protein expression of LST1 on the cell surface of mononuclear cells, and they show an inhibitory effect on lymphocyte proliferation of two LST1 proteins although they have only a very short amino acid homology.

Adjuvants, Immunologic↗
PubMed1999

pADPRT-2: a novel mammalian polymerizing(ADP-ribosyl)transferase gene related to truncated pADPRT homologues in plants and Caenorhabditis elegans.

Until recently, poly(ADP-ribosyl)ation was supposed to be confined only to polymerizing(ADP-ribosyl)transferase/(ADP-ribose)polymerase (E.C. 2.4.2.30). Here, we present novel polymerizing(ADP-ribosyl)transferase homologues from mouse and man that lack all of the N-terminal DNA binding and BRCA1 C-terminus domains and will be designated polymerizing(ADP-ribosyl)transferase-2 as distinguished from the classical polymerizing(ADP-ribosyl)transferase (polymerizing(ADP-ribosyl)transferase-1). The murine polymerizing(ADP-ribosyl)transferase-2 gene shares three identical intron positions with its Caenorhabditis elegans (EMBL nucleotide sequence database Z47075) and one with the Arabidopsis thaliana homologue ('APP', GenBank database AF069298). Expression of the murine polymerizing(ADP-ribosyl)transferase-2 gene was elevated in spleen, thymus and testis and the corresponding poly(ADP-ribosyl)ation activity might account for most of the residual poly(ADP-ribosyl)ation observed in polymerizing(ADP-ribosyl)transferase-1(-/-) mice.

Amino Acid Sequence↗
PubMed1999

Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis.

Due to their growth arrest- and apoptosis-inducing ability, glucocorticoids (GC) are widely used in the therapy of various lymphoid malignancies. Cell death is associated with activation of members of the interleukin-1beta-converting enzyme (ICE) protease/caspase family and, is presumably prevented by the anti-apoptotic protein Bcl-2. To further address the role of Bcl-2 in GC-mediated cytotoxicity, we generated subclones of the GC-sensitive human T-cell acute lymphoblastic leukemia line CCRF-CEM, in which transgenic Bcl-2 expression is regulated by tetracycline. Up to about 48 h, exogenous Bcl-2 almost completely protected these cells from apoptosis, digestion of poly-ADP ribose polymerase (PARP) and generation of Asp-Glu-Val-Asp cleaving (DEVDase) activity. However, when the cells were cultured for another 24 h in the continuous presence of GC, they underwent massive apoptosis that was associated with DEVDase activity and PARP cleavage. Bcl-2 did not markedly affect GC-mediated growth arrest, thereby separating the anti-proliferative from the apoptosis-inducing effect of GC. Moreover, Bcl-2 did not prevent the dramatic reduction in the levels of several mRNAs observed during GC treatment, including the transgenic Bcl-2 mRNA. Thus, Bcl-2 can be placed upstream of effector caspase activation, but downstream of other GC-regulated events, such as growth arrest and the potentially critical repression of steady state levels of multiple mRNA.

Apoptosis↗
PubMed1999

Poly ADP-ribosylation: a DNA break signal mechanism.

Recent evidence obtained with transgenic knockout mice suggests that the enzyme poly(ADP-ribose)polymerase (PARP) does not play a direct role in DNA break processing. Nevertheless, inactivation of the catalytic or the DNA nick-binding functions of PARP affects cellular responses to genotoxins at the level of cell survival, sister chromatid exchanges and apoptosis. In the present report, we conceptualize the idea that PARP is part of a DNA break signal mechanism. In vitro screening studies revealed the existence of a protein family containing a polymer-binding motif of about 22 amino acids. This motif is present in p53 protein as well as in MARCKS, a protein involved in the regulation of the actin cytoskeleton. Biochemical analyses showed that these sequences are directly targeted by PARP-associated polymers in vitro, and this alters several molecular functions of p53- and MARCKS protein. PARP-deficient knockout mice from transgenic mice were found to exhibit several phenotypic features compatible with altered DNA damage signaling, such as downregulation and lack of responsiveness of p53 protein to genotoxins, and morphological changes compatible with MARCKS-related cytoskeletal dysfunction. The knockout phenotype could be rescued by stable expression of the PARP gene. We propose that PARP-associated polymers may recruit signal proteins to sites of DNA breakage and reprogram their functions.

Adenosine Diphosphate Ribose↗
PubMed1998

Analysis of the TPA regulatory element in the genomic poly(ADP-ribose) synthetase gene in human leukemia U937 cells.

The human leukemia U937 cells differentiate into monocyte/macrophage-like cells when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). We observed that during this process, both protein and mRNA levels for PARS markedly decreased in U937 cells. Through deletion analysis of the PARS regulatory gene, we found that the sequence within the first intron region was responsible for the TPA-dependent repression. Electrophoretic mobility shift assays (EMSAs) and Southwestern blot analysis indicate that this element bound specifically to a nuclear protein. TPA treatment abolished the binding of the protein in U937 cells but not in HeLa cells. DNase I footprinting data show that the cis regulatory element is located between residues 328 and 383. We further examined the function of this cis element (BS207) in a basal promoter regulatory reporter construct and found that this cis element (BS207) functions as an enhancer via the binding of an unknown trans-acting factor. TPA treatment diminished the binding activity of the factor in U937 cells, resulting in a decrease in the enhanced activity to the basal level. These results suggest that abolishment of the binding of a special nuclear protein to the first intron of the PARS gene is related to the TPA-responsive downregulation of PARS in U937 cells.

Base Sequence↗
PubMed1997

p53-induced apoptosis in the human T-ALL cell line CCRF-CEM.

The tumor suppressor p53 has been implicated in apoptosis induction and is mutated in human T-ALL CCRF-CEM cells. To investigate possible consequences of wild-type p53 loss, we reconstituted CEM-C7H2, a subclone of CCRF-CEM, with a temperature-sensitive p53 allele (p53ts). Stably transfected lines expressed high levels of p53ts and shift to the permissive temperature (32 degrees C) caused rapid induction of p53-regulated genes, such as p21(CIP1/WAF1), mdm-2 and bax. This was followed by extensive apoptosis within 24 h to 36 h, supporting the notion that mutational p53 inactivation contributed to the malignant phenotype. p53-dependent apoptosis was preceded by digestion of poly(ADP-ribose) polymerase, a typical target of interleukin-1beta-converting enzyme (ICE)-like proteases/caspases, and was markedly resistant to the ICE/caspase-1 and FLICE/caspase-8 inhibitor acetyl-Tyr-Val-Ala-Asp.chloromethylketone (YVAD), but sensitive to the CPP32/caspase-3 inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp.fluoromethylketone (DEVD) and benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (zVAD), a caspase inhibitor with broader specificity. This indicated an essential involvement of caspases, but argued against a significant role of ICE/caspase-1 or FLICE/caspase-8. Actinomycin D or cycloheximide prevented cell death, suggesting that, in this system, p53-induced apoptosis depends upon macromolecule biosynthesis. Introduction of functional p53 into CEM cells enhanced their sensitivity to the DNA-damaging agent doxorubicin, but not to the tubulin-active compound vincristine. Thus, mutational p53 inactivation in ALL might entail relative resistance to DNA-damaging, but not to tubulin-destabilizing, chemotherapy.

Alleles↗
PubMed1997

The interleukin 1beta-converting enzyme inhibitor CrmA prevents Apo1/Fas- but not glucocorticoid-induced poly(ADP-ribose) polymerase cleavage and apoptosis in lymphoblastic leukemia cells.

Glucocorticoids (GC) induce programmed cell death (apoptosis) in immature lymphocytes and are an essential component in the therapy of acute lymphatic leukemia. The mechanism underlying GC-induced apoptosis particularly in leukemia cells is, however, not well understood. Most forms of apoptosis seem to employ a common final effector pathway characterized by specific proteolytic events mediated by interleukin 1beta-converting enzyme (ICE) and/or other ICE-like cysteine proteases. These events may result in the morphologic changes characteristic of apoptosis. To determine whether a similar proteolytic pathway is activated during GC-induced leukemia cell apoptosis, we investigated poly(ADP-ribose) polymerase (PARP), a typical target of ICE-like proteases, during GC-induced apoptosis of the human acute T-cell leukemic cell line CEM-C7H2. Our studies showed proteolytic PARP cleavage suggestive of activation of ICE-like proteases that preceeded morphologic signs of apoptosis. We further established stably transfected CEM-C7H2 sublines expressing the cowpox virus protein CrmA that inhibits some, but not all, ICE-like proteases. GC-induced PARP cleavage and apoptosis were neither inhibited nor delayed in crmA-expressing cell lines. In contrast, crmA expression rendered the same lines resistant to Apo1/Fas-induced PARP cleavage and apoptosis. Thus, different proteases might be activated during the effector phases of GC-and Apo1/Fas-induced apoptosis in human leukemia cells.

Apoptosis↗
PubMed1996

Characterization of detergent-solubilized beef liver mitochondrial NAD+ glycohydrolase and its truncated hydrosoluble form.

Membrane-bound beef liver mitochondrial NAD+ glycohydrolase (NADase) was partially purified after its solubilization by either detergent or crude pancreatic lipase, steapsin. Solubilization by steapsin yielded a homogeneous water-soluble enzyme. A fluorescence assay was developed that allowed visualization of NADase activity directly within the gel after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The apparent molecular masses of the detergent- and steapsin-solubilized forms were estimated to be about 30,000 and 28,000, respectively. The small part that was cleaved by steapsin represents presumably the membrane anchor of the mitochondrial NADase, as its removal converted the enzyme from a highly hydrophobic to a hydrosoluble protein. The fluorescence staining for activity was also successfully applied to other NADases. Kinetic analyses of the two forms of solubilized mitochondrial NADase revealed that the catalytic properties were unaffected after the steapsin treatment. Neither the binding affinity of the substrate analog 1, N6-etheno-NAD+ nor the inhibition by nicotinamide differed significantly between these two forms of the enzyme. Moreover, the dependence of the enzyme activity on temperature, pH, or ionic strength was also similar for both preparations. However, activity of the detergent-solubilized but not of the truncated steapsin-solubilized enzyme was strongly dependent on the presence of bivalent metal ions such as ZN2+. These results suggest that the membrane part of the mitochondrial NAD+ glycohydrolase is not required for catalysis. It appears, however, to be of importance for the regulation of the enzyme.

Animals↗
PubMed1996

Induction of endothelial cell differentiation into capillary-like structures by substance P.

Angiogenesis is an important process in inflammatory diseases and wound healing. We observed that the proinflammatory neuropeptide, substance P, stimulated angiogenesis in an in vitro model using human umbilical cord vein endothelial cells cultured on a basement membrane (Matrigel) substrate. Substance P stimulated endothelial cell differentiation into capillary-like structures in a dose-dependent manner. Stimulation of endothelial cell differentiation is a newly recognized biological function of substance P. The increased levels of substance P found in chronic inflammatory conditions may play an important role in tissue repair by promoting the development of new vessels and thus achieving compensation for ischemia.

Basement Membrane↗
PubMed1996

Modulation of Apo-1/Fas (CD95)-induced programmed cell death in myeloma cells by interferon-alpha 2.

The Apo-1/Fas (CD95) antigen is known to be involved in the process of T cell-mediated target cell killing and has recently been shown to be expressed on myeloma cell lines and native malignant plasma cells. Several cytokines have been reported to interfere with spontaneous and even Apo-1/Fas-induced apoptosis, but no attempt has been made yet to investigate these interactions and the possible underlying mechanisms in myeloma cells. Since in myeloma patients Interferon (IFN)-alpha2 displays a profound therapeutic effect in vivo, which is usually attributed to its growth inhibitory and/or immunomodulatory capacity, we set out to study the potential interference of IFN-alpha2 with Apo-1/Fas-induced apoptosis. Contrary to expectations, IFN-alpha2 reduced the degree of apoptosis caused by the treatment of five Apo-1/Fas-sensitive myeloma cell lines with a Fas monoclonal antibody (mAb). Simultaneous application of IFN-alpha2 and Fas mAb was superior to the prolonged (i.e. >8 h) preincubation with the cytokine as far as inhibition of Apo-1/Fas-induced apoptosis was concerned. This effect of IFN-alpha2 was neither explained by a down-regulation of the Apo-1/Fas receptor nor caused by modulation of the expression levels of c-myc, bcl-2-, bcl-xL, bax- or p53 genes. IFN-alpha2 did not alter the Apo-1/Fas-induced activity of Mitogen-activated protein kinase (MAPK) 1 and did not inhibit the Apo-1/Fas-mediated proteolytic cleavage of ADP-ribosyltransferase, a substrate of Interleukin-beta1 converting enzyme (ICE) and homologues. However, activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) mimicked the effects of IFN-alpha2. Furthermore, the bis-indolylmaleimide GF 109203X, a specific inhibitor of PKC, inhibited the effect of PMA as well as that of IFN-alpha2 on Apo-1/Fas-induced apoptosis. These results point to a PKC-dependent mechanism of transient interaction between the intracellular signaling along the IFN-alpha2 and the Apo-1/Fas pathway (downstream of MAPK signaling as well as of ICE homologues), which becomes exhausted by prolonged stimulation with the cytokine. According to our data IFN-alpha2, applied continuously and in high doses resembling the therapeutic situation in vivo, inhibits myeloma growth. However, based on the observed inhibitory effect of IFN-alpha2 on Apo-1/Fas-induced apoptosis, a partial inhibition of the natural immune surveillance on myeloma cells by endogenous IFN-alpha2 present in the bone marrow microenvironment of this malignancy should be investigated.

Adjuvants, Immunologic↗
PubMed1996

Prenatal effects of betamethasone-L-carnitine combinations on fetal rat lung.

Lungs of fetal rats between the 18th and 20th gestational day (total gestation lasting 22 days) were examined. There was a significant increase (p < 0.01) of the dipalmitoyl phosphatidylcholine content from day 19 to day 20 of gestation. In the second trial, pregnant rats were treated with different doses of betamethasone, L-carnitine, betamethasone-L-carnitine combinations, and saline (controls) for three days before Cesarean section on the 19th gestational day. Maternal injections of 0.10 mg/kg body weight betamethasone and 100 mg/kg body weight L-carnitine significantly (p < 0.05, p < 0.01 respectively) increased the dipalmitoyl phosphatidylcholine content of fetal lungs. Combinations of either 0.05 or 0.10 mg/kg body weight betamethasone with 100 mg L-carnitine also significantly increased the dipalmitoyl phosphatidylcholine content of the fetal lungs above control values (p < 0.001) and values achieved with betamethasone alone (p < 0.05). Maternal treatment with a betamethasone-L-carnitine combination on day 19 of gestation resulted in dipalmitoyl phosphatidylcholine levels comparable to those found on the 20th gestational day during normal lung maturation. Fetal rats delivered on the 20th gestational day survived, while fetuses delivered on the 19th gestational day did not survive.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

[Animal experiment and clinical studies of the significance of carnitine for energy metabolism in pregnant patients and the fetus during the pre- and perinatal period].

Carnitine was discovered at the beginning of this century, but was nearly forgotten until its importance in fatty acid metabolism was established 50 years later. In the past years, several other functions of carnitine in cellular metabolism have been described. The lung contains more than 40 different cell types, most of them involved in lipid metabolism. Pulmonary surfactant, a complex of 90% lipids and 10% lung specific apoproteins, is synthesized and secreated from type II cells. Surfactant is present as a monolayer at the air-liquid interface in the alveoli and decreases surface tension. Dipalmitoyl phosphatidylcholine (DPPC) is functionally and quantitatively the most important constituent of the surfactant complex. A deficiency in fetal lung surfactant is the primary cause of the respiratory distress syndrome (RDS), the most severe complication of preterm infants. Glucocorticoids are frequently used to accelerate fetal pulmonary maturation. However, a considerable number of infants fail to respond to this therapy. Maternal administration of L-carnitine significantly increased the DPPC content of fetal rat lungs. The effect of maternal treatment with a carnitine-betamethasone combination was synergistic, especially with lower betamethasone doses. Consequently the minimal dose of betamethasone which affects the DPPC content and accelerate the morphological maturation of the fetal lung was determined. This minimal dose in combination with L-carnitine increased the DPPC content on day 19 of gestation to levels found on the 20th gestational day which allows the survival of most of the preterm rats (term 22 days). Results of clinical trials show that antenatal treatment with a low dose betamethasone-L-carnitine combination has a clear advantage over standard betamethasone therapy. A multicenter study is in progress. Plasma carnitine levels at delivery are decreased to about half of the concentrations seen in non-pregnant women. Similar low levels are found only in patients with carnitine deficiency. Already in the 12th week of gestation the mean whole blood and plasma carnitine levels were found to be significantly lower than those of controls. The reason for increased excretion of acylcarnitines during pregnancy is not known, but could be a detoxifying function similar to that found in patients with inborn errors of fatty acid metabolism and organic acidurias. Carnitine substitution (1 g daily) from the 20th gestational week up to parturition resulted in an increase of free carnitine levels in maternal plasma. A dosage of 0.5 g/day was without effect. Prolonged substitution in pregnant women, especially in risk pregnancies may be preferable to high doses of carnitine administered shortly before imminent premature delivery.

Animals↗
PubMed1995

Identification and purification of a bovine liver mitochondrial NAD(+)-glycohydrolase.

Nonenzymatic ADP-ribosylation of mitochondrial proteins is thought to play a role in the regulation of Ca2+ efflux from mitochondria. It has been shown that intramitochondrial ADP-ribose is generated by a specific NAD(+)glycohydrolase, which catalizes hydrolysis of NAD+ to ADP-ribose and nicotinamide. We purified this enzyme from bovine liver mitochondrial membranes. The final preparation had a 1660-fold purified enzyme activity and contained a main protein band with an apparent molar mass of 32,000 in a SDS-polyacrylamide gel. The identity of this protein band with NAD(+)-glycohydrolase was verified by renaturation of its enzymatic activity. Partial amino acid sequence information was obtained from two enzyme fragments after proteolytic cleavage of the protein band in the SDS-polyacrylamide gel. Searches in protein databases revealed that an arginine ADP-ribosyl hydrolase harbours two stretches of amino acids that are highly similar to the partial NAD(+)-glycohydrolase sequences.

Amino Acid Sequence↗
PubMed1995

Specific neurotrophin binding to leucine-rich motif peptides of TrkA and TrkB.

The extracellular domains of the TrkA and TrkB neurotrophin receptors contain defined structural modules such as immunoglobulin-like domains and leucine-rich motifs (LRMs) [Schneider and Schweiger, Oncogene 6 (1991) 1807-1811]. Recently, the second LRM of TrkA was identified as a functional nerve growth factor (NGF) binding site [Windisch et al, J. Biol. chem. (1995) in press]. A peptide corresponding to this region effectively bound NGF and blocked binding of NGF to the recombinant extracellular domain of TrkA. The corresponding TrkB peptide exhibited the same effects with respect to brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), indicating that all three TrkB ligands utilize this same binding site. Isolated LRMs therefore embody independent functional entities.

Amino Acid Sequence↗
PubMed1995

Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 bind to a single leucine-rich motif of TrkB.

TrkB is a member of the Trk family of neurotrophin receptors. Its extracellular domain exhibits the same modular structure found in its homologs, TrkA and TrkC, consisting of an N-terminal LRM3 cassette and two immunoglobulin-like modules (Ig2 domain) adjacent to the membrane. The LRM3 cassette comprises two cysteine-rich clusters framing a tandem array of three leucine-rich motifs (LRMs). On the basis of the recent identification of a nerve growth factor (NGF) binding site within TrkA, the ability of the different structural entities within the extracellular domain of TrkB to bind the various neurotrophins was determined by using a recombinant receptor approach. Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) bound to the LRM3 cassette of TrkB, whereas NGF did not. These binding characteristics evidently reflect in vivo specificities. A more precise mapping of the region(s) responsible for binding BDNF, NT-3, and NT-4 identified the second leucine-rich motif of TrkB as a functional unit capable of binding all three neurotrophins. The affinities and kinetics that this short stretch of amino acids exhibited with respect to the different neurotrophins were clearly akin to those observed for cells ectopically expressing TrkB receptors. With 24 amino acids determining the affinities and kinetics of the interactions with three different partners, the leucine-rich motif is strongly established as one of the most potent and flexible protein--protein interaction motifs.

Amino Acid Sequence↗
PubMed1995

Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease.

Poly(ADP-ribosyl)ation is catalyzed by NAD+: protein(ADP-ribosyl) transferase (ADPRT), a chromatin-associated enzyme which, in the presence of DNA breaks, transfers ADP-ribose from NAD+ to nuclear proteins. This post-translational modification has been implicated in many fundamental processes, like DNA repair, chromatin stability, cell proliferation, and cell death. To elucidate the biological function of ADPRT and poly(ADP-ribosyl)ation in vivo the gene was inactivated in the mouse germ line. Mice homozygous for the ADPRT mutation are healthy and fertile. Analysis of mutant tissues and fibroblasts isolated from mutant fetuses revealed the absence of ADPRT enzymatic activity and poly(ADP-ribose), implying that no poly(ADP-ribosyl)ated proteins are present. Mutant embryonic fibroblasts were able to efficiently repair DNA damaged by UV and alkylating agents. However, proliferation of mutant primary fibroblasts as well as thymocytes following gamma-radiation in vivo was impaired. Moreover, mutant mice are susceptible to the spontaneous development of skin disease as approximately 30% of older mice develop epidermal hyperplasia. The generation of viable ADPRT-/-mice negates an essential role for this enzyme in normal chromatin function, but the impaired proliferation and the onset of skin lesions in older mice suggest a function for ADPRT in response to environmental stress.

Animals↗
PubMed1995

On the biological role of the nuclear polymerizing NAD+: protein(ADP-ribosyl) transferase (ADPRT): ADPRT from Dictyostelium discoideum and inactivation of the ADPRT gene in the mouse.

Two approaches have been used to elucidate the role of the nuclear polymerizing NAD+:protein(ADP-ribosyl)-transferase (ADPRT): i) comparison of the primary structure of Dictyostelium discoideum ADPRT derived from a 2 kb, partial cDNA sequence with the mammalian, fish, amphibian and insect counterparts revealed an overall homology of 25%. Whereas the automodification domain was not conserved at all, the NAD+ binding domain (aa 859-908) showed more than 70% identical amino acids in all species. Together with the similar enzymatic properties of the ADPRTs the genetic conservation underlined the notion that ADPRT plays a major role in various cellular processes; and ii) inactivation of the ADPRT gene in murine embryonic stem cells by homologous recombination led to mouse strains with a complete lack of nuclear poly(ADP-ribosyl)ation. These ADPRT mutant mice were viable and fertile indicating that ADPRT is dispensable in mouse development. Moreover, repair of UV and MNNG induced DNA damage was not affected in ADPRT/3T3 like fibroblasts, as measured by reactivation of in vitro damaged reporter plasmids and unscheduled DNA synthesis. However, about 30% of the ADPRT mutant mice developed pathological skin aberrations on a mixed 129/Sv x C57B1/6 genetic background. These mice will be extremely useful to define the precise biological role of poly(ADP-ribosyl)ation.

ADP Ribose Transferases↗