TY - JOUR
T1 - Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome
AU - Zhang, Bin
AU - Jain, Sanjay
AU - Song, Haengseok
AU - Fu, Ming
AU - Heuckeroth, Robert O.
AU - Erlich, Jonathan M.
AU - Jay, Patrick Y.
AU - Milbrandt, Jeffrey
PY - 2007/9
Y1 - 2007/9
N2 - PDS5B is a sister chromatid cohesion protein that is crucial for faithful segregation of duplicated chromosomes in lower organisms. Mutations in cohesion proteins are associated with the developmental disorder Cornelia de Lange syndrome (CdLS) in humans. To delineate the physiological roles of PDS5B in mammals, we generated mice lacking PDS5B (APRIN). Pds5B-deficient mice died shortly after birth. They exhibited multiple congenital anomalies, including heart defects, cleft palate, fusion of the ribs, short limbs, distal colon aganglionosis, abnormal migration and axonal projections of sympathetic neurons, and germ cell depletion, many of which are similar to abnormalities found in humans with CdLS. Unexpectedly, we found no cohesion defects in Pds5B-/- cells and detected high PDS5B expression in post-mitotic neurons in the brain. These results, along with the developmental anomalies of Pds5B-/- mice, the presence of a DNA-binding domain in PDS5B in vertebrates and its nucleolar localization, suggest that PDS5B and the cohesin complex have important functions beyond their role in chromosomal dynamics.
AB - PDS5B is a sister chromatid cohesion protein that is crucial for faithful segregation of duplicated chromosomes in lower organisms. Mutations in cohesion proteins are associated with the developmental disorder Cornelia de Lange syndrome (CdLS) in humans. To delineate the physiological roles of PDS5B in mammals, we generated mice lacking PDS5B (APRIN). Pds5B-deficient mice died shortly after birth. They exhibited multiple congenital anomalies, including heart defects, cleft palate, fusion of the ribs, short limbs, distal colon aganglionosis, abnormal migration and axonal projections of sympathetic neurons, and germ cell depletion, many of which are similar to abnormalities found in humans with CdLS. Unexpectedly, we found no cohesion defects in Pds5B-/- cells and detected high PDS5B expression in post-mitotic neurons in the brain. These results, along with the developmental anomalies of Pds5B-/- mice, the presence of a DNA-binding domain in PDS5B in vertebrates and its nucleolar localization, suggest that PDS5B and the cohesin complex have important functions beyond their role in chromosomal dynamics.
KW - APRIN
KW - Congenital defects
KW - Cornelia de Lange syndrome
KW - Mouse
KW - PDS5
KW - Primordial germ cells
KW - Sister chromatid cohesion
UR - http://www.scopus.com/inward/record.url?scp=34848911616&partnerID=8YFLogxK
U2 - 10.1242/dev.005884
DO - 10.1242/dev.005884
M3 - Article
C2 - 17652350
AN - SCOPUS:34848911616
SN - 0950-1991
VL - 134
SP - 3191
EP - 3201
JO - Development
JF - Development
IS - 17
ER -