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Hematological shift in goat kids naturally devoid of prion protein.

Reiten MR, Bakkebø MK, Brun-Hansen H, Lewandowska-Sabat AM, Olsaker I, Tranulis MA, Espenes A, Boysen P - Front Cell Dev Biol (2015)

Bottom Line: Morphological investigations of blood smears and bone marrow imprints did not reveal irregularities.Studies of relative composition of PBMCs, phagocytic ability of monocytes and T-cell proliferation revealed no significant differences between the genotypes.Our data suggest that PrP(C) has a role in bone marrow physiology and warrant further studies of PrP(C) in erythroid and immune cell progenitors as well as differentiated effector cells also under stressful conditions.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences Oslo, Norway.

ABSTRACT
The physiological role of the cellular prion protein (PrP(C)) is incompletely understood. The expression of PrP(C) in hematopoietic stem cells and immune cells suggests a role in the development of these cells, and in PrP(C) knockout animals altered immune cell proliferation and phagocytic function have been observed. Recently, a spontaneous nonsense mutation at codon 32 in the PRNP gene in goats of the Norwegian Dairy breed was discovered, rendering homozygous animals devoid of PrP(C). Here we report hematological and immunological analyses of homozygous goat kids lacking PrP(C) (PRNP(Ter/Ter) ) compared to heterozygous (PRNP (+/Ter)) and normal (PRNP (+/+)) kids. Levels of cell surface PrP(C) and PRNP mRNA in peripheral blood mononuclear cells (PBMCs) correlated well and were very low in PRNP (Ter/Ter), intermediate in PRNP (+/Ter) and high in PRNP (+/+) kids. The PRNP (Ter/Ter) animals had a shift in blood cell composition with an elevated number of red blood cells (RBCs) and a tendency toward a smaller mean RBC volume (P = 0.08) and an increased number of neutrophils (P = 0.068), all values within the reference ranges. Morphological investigations of blood smears and bone marrow imprints did not reveal irregularities. Studies of relative composition of PBMCs, phagocytic ability of monocytes and T-cell proliferation revealed no significant differences between the genotypes. Our data suggest that PrP(C) has a role in bone marrow physiology and warrant further studies of PrP(C) in erythroid and immune cell progenitors as well as differentiated effector cells also under stressful conditions. Altogether, this genetically unmanipulated PrP(C)-free animal model represents a unique opportunity to unveil the enigmatic physiology and function of PrP(C).

No MeSH data available.


Lymphocyte proliferation test. Proliferation of T cells after 72 h stimulation with (A) Con A, (B) IL-2, and (C) IL-15, measured as beta emission following DNA incorporation of tritiated thymidine (net CPM = sample CPM − control CPM). In all cases n = 8.
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Figure 5: Lymphocyte proliferation test. Proliferation of T cells after 72 h stimulation with (A) Con A, (B) IL-2, and (C) IL-15, measured as beta emission following DNA incorporation of tritiated thymidine (net CPM = sample CPM − control CPM). In all cases n = 8.

Mentions: To investigate if PrPC expression could be involved in cellular proliferation, we stimulated PBMCs in vitro using the mitogen Con A or the cytokines IL-2 or IL-15 to cover proliferation of T cells and NK cells/innate lymphocytes (Figure 5). The cell cultures proliferated well in response to these stimuli, but no significant differences between the groups were observed, although a slightly higher median response of cells from the PRNPTer/Ter group was noted for all stimulations.


Hematological shift in goat kids naturally devoid of prion protein.

Reiten MR, Bakkebø MK, Brun-Hansen H, Lewandowska-Sabat AM, Olsaker I, Tranulis MA, Espenes A, Boysen P - Front Cell Dev Biol (2015)

Lymphocyte proliferation test. Proliferation of T cells after 72 h stimulation with (A) Con A, (B) IL-2, and (C) IL-15, measured as beta emission following DNA incorporation of tritiated thymidine (net CPM = sample CPM − control CPM). In all cases n = 8.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495340&req=5

Figure 5: Lymphocyte proliferation test. Proliferation of T cells after 72 h stimulation with (A) Con A, (B) IL-2, and (C) IL-15, measured as beta emission following DNA incorporation of tritiated thymidine (net CPM = sample CPM − control CPM). In all cases n = 8.
Mentions: To investigate if PrPC expression could be involved in cellular proliferation, we stimulated PBMCs in vitro using the mitogen Con A or the cytokines IL-2 or IL-15 to cover proliferation of T cells and NK cells/innate lymphocytes (Figure 5). The cell cultures proliferated well in response to these stimuli, but no significant differences between the groups were observed, although a slightly higher median response of cells from the PRNPTer/Ter group was noted for all stimulations.

Bottom Line: Morphological investigations of blood smears and bone marrow imprints did not reveal irregularities.Studies of relative composition of PBMCs, phagocytic ability of monocytes and T-cell proliferation revealed no significant differences between the genotypes.Our data suggest that PrP(C) has a role in bone marrow physiology and warrant further studies of PrP(C) in erythroid and immune cell progenitors as well as differentiated effector cells also under stressful conditions.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences Oslo, Norway.

ABSTRACT
The physiological role of the cellular prion protein (PrP(C)) is incompletely understood. The expression of PrP(C) in hematopoietic stem cells and immune cells suggests a role in the development of these cells, and in PrP(C) knockout animals altered immune cell proliferation and phagocytic function have been observed. Recently, a spontaneous nonsense mutation at codon 32 in the PRNP gene in goats of the Norwegian Dairy breed was discovered, rendering homozygous animals devoid of PrP(C). Here we report hematological and immunological analyses of homozygous goat kids lacking PrP(C) (PRNP(Ter/Ter) ) compared to heterozygous (PRNP (+/Ter)) and normal (PRNP (+/+)) kids. Levels of cell surface PrP(C) and PRNP mRNA in peripheral blood mononuclear cells (PBMCs) correlated well and were very low in PRNP (Ter/Ter), intermediate in PRNP (+/Ter) and high in PRNP (+/+) kids. The PRNP (Ter/Ter) animals had a shift in blood cell composition with an elevated number of red blood cells (RBCs) and a tendency toward a smaller mean RBC volume (P = 0.08) and an increased number of neutrophils (P = 0.068), all values within the reference ranges. Morphological investigations of blood smears and bone marrow imprints did not reveal irregularities. Studies of relative composition of PBMCs, phagocytic ability of monocytes and T-cell proliferation revealed no significant differences between the genotypes. Our data suggest that PrP(C) has a role in bone marrow physiology and warrant further studies of PrP(C) in erythroid and immune cell progenitors as well as differentiated effector cells also under stressful conditions. Altogether, this genetically unmanipulated PrP(C)-free animal model represents a unique opportunity to unveil the enigmatic physiology and function of PrP(C).

No MeSH data available.