title: Hematopoietic lineage skewing and intestinal epithelia degeneration in aged mice with telomerase RNA component deletion.
abstract: A deletion of a telomerase RNA component (Terc(-/-)) in C57BL/6 (B6) mice resulted in hematopoietic lineage skewing with increased neutrophils and CD11b(+) myeloid cells and decreased red blood cells and CD45R(+) B lymphocytes when animals reach ages older than 12 months. There was no decline in bone marrow (BM) c-Kit(+)Sca-1(+)Lin(-) (KSL) cells in old Terc(-/-) mice, and the lineage skewing phenomenon was not transferred when BM cells from old Terc(-/-) donors were transplanted into young B6 recipients. Necropsy and histological examinations found minimal to no change in the lung, spleen and liver but detected severe epithelia degeneration, ulceration and infection in small and large intestines, leading to enteritis, typhlitis and colitis in old Terc(-/-) mice. In a mouse model of dextran-sulfate-sodium-induced typhlitis and colitis, development of intestinal pathology was associated with increases in neutrophils and CD11b(+) myeloid cells and a decrease in CD45R(+) B cells, similar to those observed in old Terc(-/-) mice. Treatment of 11-13 month old Terc(-/-) mice with antibiotic trimethoprim-sulfa water reduced neutrophils and myeloid cells and increased B lymphocytes in the blood, indicating that mitigation of intestinal infection and inflammation could alleviate hematological abnormalities in old Terc(-/-) animals.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: chenji@nhlbi.nih.gov.
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bryant
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: Dent
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States; Hematology Department, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Desierto
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000235:genetics*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D017384:Sequence Deletion; D019098:Telomerase / Q000235:genetics*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
chemical_list: C422952:telomerase RNA; D012313:RNA; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D019098:Telomerase
keywords: Aging; Flow cytometry; Hematopoietic lineage skewing; Histology; Intestinal epithelia degeneration; Terc(−/−) mice