Hematological shift in goat kids naturally devoid of prion protein

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 PRNPTer/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 .