Hematological Changes in Aging Male C57BL/6 Jax Mice

Ewing, Keith L.; Tauber, Oscar E.

doi:10.1093/geronj/19.2.165

Cited by 18 publications

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“…Between 28 and 60 days a very small number of anacmic mice (four males out of approximately Is0 males and females studied) died. The rest-the great majority-survived and their haemoglobin levels 039 0 4 5 0 5 5 0 6 0 078 0 7 6 0 8 8 090 041 0 5 4 062 concentration over the same period in normal mice; this has been noted by others (Strong and Francis, 1940; Ewing and Tauber, 1964). While young heterozygous females show a mean haemoglobin level slightly lower than that of normal males, this difference is no longer apparent after the age of 40 days.…”

Section: Huerimtological Findingssupporting

confidence: 51%

X‐Linked Hypochromic Anaemia of Mice

Bannerman

Pinkerton

1967

Br J Haematol

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MANY different imitations giving rise to anaemia in mice have now bccn rcportcd and their genctic and hacmatological features have recently been reviewed (Russell and Bcrnstein, I 966; I'inkerton and Bannerman, 1967). In some instances, such as the hereditary spherocytosis of the deer mouse and the autoimmune hacmolytic anaemia of the NZUjB1 strain of house mouse, they mimic human disorders, and their study offers the possibility of insight into mechanisms of human disease. Other mutants provide the opportunity to isolatc and study single, genetically-controlled, steps in haemopoiesis. Sex-linked (or, preferably, X-linked) anaemia of mice (gene symbol, sla) first appeared in the male offspring of the daughter of a male who was irradiated with 5 0 0 r. of X-rays, and this finding and the results of subsequent linkage studies were reported by Falconer and Isaacson (1962). Grewal (1962) gave a general description of the anaemia and compared it with thalassaemia. We have reported preliminary findings on the nature and mechanism of the anaemia Cooper, 1964, 1966; Pinkerton, Kreimer-Uirnbaum and Bannerman, 1966), and we now describe in detail the haematological findings, including the effects of age and various forms of treatment, and discuss possible analogies between X-linked mouse anaemia and the human hypochromic anaemias. MATERIALS AND METHODSThc mice studied were descendants of a small breeding stock from a mixed strain, kindly presented by Dr. D. S. Falconer. Most of the investigations reported here have been carried out on animals inbred from the original stock by brother-sister matings. It has sometimes been necessary to use as controls normal first generation hybrid males from crosses with the inbred C~7B1/6 Jax strain; this has been occasioned by the presence in our original stock of the X-linked mutation, 'Brindled', lethal shortly after birth in the male, in repulsion to sla (to which it is quite closely linked; Falconer and Isaacson, 1962). Although strain differences may affect the blood picture in mice (Russell, Neufeld and Higgins, 1951), careful comparison between normal non-anaemic males of our partially inbred strain and the first generation hybrids with the C57B1/6 Jax strain revealed no detectable differences.The animals were maintained on Rockland rat and mouse diet, the constitution of which is shown in Table I; tap water was given ad libitum Body weights were regularly recorded to the nearest 0.1 g.Serial observations were made from the time of weaning (21-28 days) to more than 300 days of age in 64 anaemic hemizygous male mice, 45 homozygous female mice, 69 heterozygous female carriers and I I I normal male mice of the mixed strain or the hybrid mentioned above.

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Section: Huerimtological Findingssupporting

confidence: 51%

X‐Linked Hypochromic Anaemia of Mice

Bannerman

Pinkerton

1967

Br J Haematol

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“…Analysis of the blood parameters also demonstrated that 2 yrs old TA-65 treated mice present higher levels of RBC and hemoglobin comparing to the control cohorts. The decrease of such parameters is a regular situation experienced during aging progression in healthy old mice and could be related to RBC fragility and deficient regulation of the stem cell pools (Ewing & Tauber 1964; Finch & Foster 1973; Tyan 1980; Tyan 1982a; Tyan 1982b; Xing et al . 2006).…”

Section: Discussionmentioning

confidence: 99%

The telomerase activator TA‐65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence

et al. 2011

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SummaryHere, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc + ⁄ ) MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc ) ⁄ ) littermateMEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.

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“…In striking contrast, a large number of DNA methylated genes were exclusively expressed in downstream progenitor and effector cells, but not in HSCs themselves (Figure 2D). Among this latter class were genes important for the development, specification, and function of diverse hematopoietic cell types, including lymphoid and erythroid lineages, both of which are diminished upon hematopoietic aging in mouse and man (Figures 1C and S1D) (Beerman et al, 2010b;Ewing and Tauber, 1964). For example, old HSCs showed significant gains of DNA methylation at the core promoter of Blnk, a signal adaptor molecule that is required for B cell development (Pappu et al, 1999) and only expressed downstream of HSCs in the B cell lineage starting at the CLP stage (Figure 2E).…”

Section: Dna Methylation Changes During Hsc Ontogeny Largely Target Genes Expressed In Downstream Hematopoietic Progenymentioning

confidence: 99%

Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging

et al. 2013

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The functional potential of hematopoietic stem cells (HSCs) declines during aging, and in doing so, significantly contributes to hematopoietic pathophysiology in the elderly. To explore the relationship between age-associated HSC decline and the epigenome, we examined global DNA methylation of HSCs during ontogeny in combination with functional analysis. Although the DNA methylome is generally stable during aging, site-specific alterations of DNA methylation occur at genomic regions associated with hematopoietic lineage potential and selectively target genes expressed in downstream progenitor and effector cells. We found that age-associated HSC decline, replicative limits, and DNA methylation are largely dependent on the proliferative history of HSCs, yet appear to be telomere-length independent. Physiological aging and experimentally enforced proliferation of HSCs both led to DNA hypermethylation of genes regulated by Polycomb Repressive Complex 2. Our results provide evidence that epigenomic alterations of the DNA methylation landscape contribute to the functional decline of HSCs during aging.

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Hematological Changes in Aging Male C57BL/6 Jax Mice

Cited by 18 publications

References 0 publications

X‐Linked Hypochromic Anaemia of Mice

X‐Linked Hypochromic Anaemia of Mice

The telomerase activator TA‐65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence

Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging

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