TY - JOUR
T1 - Spontaneous 8bp deletion in Nbeal2 recapitulates the gray platelet syndrome in mice
AU - Tomberg, Kärt
AU - Khoriaty, Rami
AU - Westrick, Randal J.
AU - Fairfield, Heather E.
AU - Reinholdt, Laura G.
AU - Brodsky, Gary L.
AU - Davizon-Castillo, Pavel
AU - Ginsburg, David
AU - Di Paola, Jorge
N1 - Publisher Copyright:
© 2016 Tomberget al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/3
Y1 - 2016/3
N2 - During the analysis of a whole genome ENU mutagenesis screen for thrombosis modifiers, a spontaneous 8 base pair (bp) deletion causing a frameshift in exon 27 of the Nbeal2 gene was identified. Though initially considered as a plausible thrombosis modifier, this Nbeal2 mutation failed to suppre the synthetic lethal thrombosis on which the original ENU screen was based. Mutations in NBEAL2 cause Gray Platelet Syndrome (GPS), an autosomal receive bleeding disorder characterized by macrothrombocytopenia and grayappearing platelets due to lack of platelet alpha granules. Mice homozygous for the Nbeal2 8 bp deletion (Nbeal2GPS/GPS) exhibit a phenotype similar to human GPS, with significantly reduced platelet counts compared to littermate controls (p = 1.63 × 10-7). Nbeal2GPS/GPS mice also have markedly reduced numbers of platelet alpha granules and an increased level of emperipolesis, consistent with previously characterized mice carrying targeted Nbeal2 null alleles. These findings confirm previous reports, provide an additional mouse model for GPS, and highlight the potentially confounding effect of background spontaneous mutation events in well-characterized mouse strains.
AB - During the analysis of a whole genome ENU mutagenesis screen for thrombosis modifiers, a spontaneous 8 base pair (bp) deletion causing a frameshift in exon 27 of the Nbeal2 gene was identified. Though initially considered as a plausible thrombosis modifier, this Nbeal2 mutation failed to suppre the synthetic lethal thrombosis on which the original ENU screen was based. Mutations in NBEAL2 cause Gray Platelet Syndrome (GPS), an autosomal receive bleeding disorder characterized by macrothrombocytopenia and grayappearing platelets due to lack of platelet alpha granules. Mice homozygous for the Nbeal2 8 bp deletion (Nbeal2GPS/GPS) exhibit a phenotype similar to human GPS, with significantly reduced platelet counts compared to littermate controls (p = 1.63 × 10-7). Nbeal2GPS/GPS mice also have markedly reduced numbers of platelet alpha granules and an increased level of emperipolesis, consistent with previously characterized mice carrying targeted Nbeal2 null alleles. These findings confirm previous reports, provide an additional mouse model for GPS, and highlight the potentially confounding effect of background spontaneous mutation events in well-characterized mouse strains.
UR - http://www.scopus.com/inward/record.url?scp=84960976450&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0150852
DO - 10.1371/journal.pone.0150852
M3 - Article
C2 - 26950939
AN - SCOPUS:84960976450
VL - 11
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
M1 - e0150852
ER -