Gabriele Hoelzlwimmer

Publications (2)12.79 Total impact

• Source

  Available from: Silke H Raffegerst

  Article: Diverse hematological malignancies including hodgkin-like lymphomas develop in chimeric MHC class II transgenic mice.

  Silke H Raffegerst, Gabriele Hoelzlwimmer, Sandra Kunder, Josef Mysliwietz, Leticia Quintanilla-Martinez, Dolores J Schendel
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  ABSTRACT: A chimeric HLA-DR4-H2-E (DR4) homozygous transgenic mouse line spontaneously develops diverse hematological malignancies with high frequency (70%). The majority of malignancies were distributed equally between T and B cell neoplasms and included lymphoblastic T cell lymphoma (LTCL), lymphoblastic B cell lymphoma (LBCL), diffuse large B cell lymphoma (DLBCL), the histiocyte/T cell rich variant of DLBCL (DLBCL-HA/T cell rich DLBCL), splenic marginal zone lymphoma (SMZL), follicular B cell lymphoma (FBL) and plasmacytoma (PCT). Most of these neoplasms were highly similar to human diseases. Also, some non-lymphoid malignancies such as acute myeloid leukemia (AML) and histiocytic sarcoma were found. Interestingly, composite lymphomas, including Hodgkin-like lymphomas, were also detected that had CD30(+) Hodgkin/Reed-Sternberg (H/RS)-like cells, representing a tumor type not previously described in mice. Analysis of microdissected H/RS-like cells revealed their origin as germinal center B cells bearing somatic hypermutations and, in some instances, crippled mutations, as described for human Hodgkin lymphoma (HL). Transgene integration in an oncogene was excluded as an exclusive driving force of tumorigenesis and age-related lymphoma development suggests a multi-step process. Thus, this DR4 line is a useful model to investigate common molecular mechanisms that may contribute to important neoplastic diseases in man.
  PLoS ONE 01/2009; 4(12):e8539. · 4.09 Impact Factor
• Source

  Available from: Gerhard Przemeck

  Article: ER stress-mediated apoptosis in a new mouse model of osteogenesis imperfecta.

  Thomas S Lisse, Frank Thiele, Helmut Fuchs, Wolfgang Hans, Gerhard K H Przemeck, Koichiro Abe, Birgit Rathkolb, Leticia Quintanilla-Martinez, Gabriele Hoelzlwimmer, Miep Helfrich, Eckhard Wolf, Stuart H Ralston, Martin Hrabé de Angelis
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  ABSTRACT: Osteogenesis imperfecta is an inherited disorder characterized by increased bone fragility, fractures, and osteoporosis, and most cases are caused by mutations affecting the type I collagen genes. Here, we describe a new mouse model for Osteogenesis imperfecta termed Aga2 (abnormal gait 2) that was isolated from the Munich N-ethyl-N-nitrosourea mutagenesis program and exhibited phenotypic variability, including reduced bone mass, multiple fractures, and early lethality. The causal gene was mapped to Chromosome 11 by linkage analysis, and a C-terminal frameshift mutation was identified in the Col1a1 (procollagen type I, alpha 1) gene as the cause of the disorder. Aga2 heterozygous animals had markedly increased bone turnover and a disrupted native collagen network. Further studies showed that abnormal proalpha1(I) chains accumulated intracellularly in Aga2/+ dermal fibroblasts and were poorly secreted extracellularly. This was associated with the induction of an endoplasmic reticulum stress-specific unfolded protein response involving upregulation of BiP, Hsp47, and Gadd153 with caspases-12 and -3 activation and apoptosis of osteoblasts both in vitro and in vivo. These studies resulted in the identification of a new model for Osteogenesis imperfecta, and identified a role for intracellular modulation of the endoplasmic reticulum stress-associated unfolded protein response machinery toward osteoblast apoptosis during the pathogenesis of disease.
  PLoS Genetics 03/2008; 4(2):e7. · 8.69 Impact Factor