Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome

Development. 2007 Sep;134(17):3191-201. doi: 10.1242/dev.005884. Epub 2007 Jul 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Body Patterning / genetics
  • Bone and Bones / abnormalities
  • Bone and Bones / embryology
  • Cell Proliferation
  • Cleft Palate / embryology
  • Cleft Palate / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • De Lange Syndrome / embryology
  • De Lange Syndrome / pathology*
  • Germ Cells / cytology
  • Heart / embryology
  • Heart Defects, Congenital / embryology
  • Heart Defects, Congenital / genetics
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Nude
  • Peripheral Nervous System / abnormalities
  • Peripheral Nervous System / embryology
  • Sister Chromatid Exchange / genetics
  • Sister Chromatid Exchange / physiology
  • Transcription Factors / genetics*
  • Transcription Factors / physiology


  • DNA-Binding Proteins
  • PDS5B protein, mouse
  • Transcription Factors