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Full-Text Articles in Medical Sciences

A Novel Transgenic Line Of Mice Exhibiting Autosomal Recessive Male-Specific Lethality And Non-Alcoholic Fatty Liver Disease, Vincent Sollars, Benjamin Mcentee, Julie Engiles, Jay Rothstein, Arthur Buchberg Aug 2012

A Novel Transgenic Line Of Mice Exhibiting Autosomal Recessive Male-Specific Lethality And Non-Alcoholic Fatty Liver Disease, Vincent Sollars, Benjamin Mcentee, Julie Engiles, Jay Rothstein, Arthur Buchberg

Vincent E Sollars

We have isolated a Meis1a transgenic mouse line exhibiting recessive male-specific lethality and nonalcoholic fatty liver disease (NAFLD), which coincides with pubescence and is androgen-dependent. The phenotype is due to disruption of an endogenous locus, since other Meis1a transgenic lines do not exhibit these phenotypes. Necropsy analysis revealed hepatic microvesicular steatosis in pubescent male homozygous mice, which is absent in transgenic females. The transgene insertion site was localized to chromosome 1 and further refined by cloning the flanking regions. Sequence analysis shows that the integration site disrupts a putative metallo-b-lactamase gene with a 21.3 kb deletion encompassing exons 5–7.


Analysis Of Expansion Of Myeloid Progenitors In Mice To Identify Leukemic Susceptibility Genes, Vincent Sollars, Ed Pequignot, Jay Rothstein, Arthur Buchberg Aug 2012

Analysis Of Expansion Of Myeloid Progenitors In Mice To Identify Leukemic Susceptibility Genes, Vincent Sollars, Ed Pequignot, Jay Rothstein, Arthur Buchberg

Vincent E Sollars

The myeloid progenitor cell compartment (MPC) exhibits pronounced expansion in human myeloid leukemias. It is becoming more apparent that progression of myelodysplastic syndromes and myeloproliferative diseases to acute myelogenous leukemia is the result of defects in progenitor cell maturation. The MPC of bone marrow was analyzed in mice using a cell culture assay for measuring the relative frequency of proliferative myeloid progenitors. Response to the cytokines SCF, IL-3, and GMCSF was determined by this assay for the leukemic mouse strain BXH-2 and ten other inbred mouse strains. Significant differences were found to exist among ten inbred mouse strains in the …


Defect In Early Lung Defence Against Pseudomonas Aeruginosa In Dba/2 Mice Is Associated With Acute Inflammatory Lung Injury And Reduced Bactericidal Activity In Naive Macrophages, Kari Wilson,, Jennifer Napper,, James Denvir, Vincent Sollars, Hongwei Yu Aug 2012

Defect In Early Lung Defence Against Pseudomonas Aeruginosa In Dba/2 Mice Is Associated With Acute Inflammatory Lung Injury And Reduced Bactericidal Activity In Naive Macrophages, Kari Wilson,, Jennifer Napper,, James Denvir, Vincent Sollars, Hongwei Yu

Vincent E Sollars

Pseudomonas aeruginosa is an opportunistic pathogen that causes serious respiratory disease in the immune-compromised host. Using an aerosol infection model, 11 inbred mouse strains (129/Sv, A/J, BALB/c, C3H/HeN, C57BL/6, DBA/2, FVB, B10.D2/oSnJ, B10.D2/nSnJ, AKR/J and SWR/J) were tested for increased susceptibility to P. aeruginosa lung colonization. DBA/2 was the only mouse strain that had increased bacterial counts in the lung within 6 h post-infection. This deficiency incited a marked inflammatory response with reduced bacterial lung clearance and a mortality rate of 96.7 %. DBA/2 mice displayed progressive deterioration of lung pathology with extensive alveolar exudate and oedema formation at 48–72 …


Ybx1 Expression And Function In Early Hematopoiesis And Leukemic Cells, Jasjeet Bhullar, Vincent Sollars Aug 2012

Ybx1 Expression And Function In Early Hematopoiesis And Leukemic Cells, Jasjeet Bhullar, Vincent Sollars

Vincent E Sollars

Hematopoietic transcription factors play a critical role in directing the commitment and differentiation of hematopoietic stem cells along a particular lineage. Y-box protein (YBX1) is a transcription factor which is widely expressed throughout development and is involved in erythroid cell development; however, its role in early hematopoietic differentiation is not known. This study aims to investigate the role of YBX1 expression in early hematopoietic differentiation and leukemia. Here, we show that YBX1 is highly expressed in mouse erythroid myeloid lymphoid-clone 1 (EML), a hematopoietic precursor cell line, but is down-regulated in myeloid progenitors and GM-CSF-treated EML cells during the course …


Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles Aug 2012

Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles

Vincent E Sollars

Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-β2 (RAR-β2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-β2. There was not a strict correlation between DNA methylation of RAR-β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-β gene promoter was higher in cells expressing RAR-β2. All trans retinoic acid treatment of …


Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent Sollars, Andrea Belalcazar Aug 2012

Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent Sollars, Andrea Belalcazar

Vincent E Sollars

Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …


Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas Ruden, Mark Garfinkel, Vincent Sollars, Xiangyi Lu Aug 2012

Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas Ruden, Mark Garfinkel, Vincent Sollars, Xiangyi Lu

Vincent E Sollars

Conrad Waddington published an influential model for evolution in his 1942 paper, Canalization of Development and Inheritance of Acquired Characters. In this classic, albeit controversial, paper, he proposed that an unknown mechanism exists that conceals phenotypic variation until the organism is stressed. Recent studies have proposed that the highly conserved chaperone Hsp90 could function as a “capacitor,” or an “adaptively inducible canalizer,” that masks silent phenotypic variation of either genetic or epigenetic origin. This review will discuss evidence for, and arguments against, the role of Hsp90 as a capacitor for morphological evolution, and as a key component of what we …