title: Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease.
abstract: BACKGROUND
  Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD.
  
  
  RESULTS
  We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths.
  
  
  CONCLUSIONS
  Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron.
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California, Gross Hall 1130, Mail Code, 4086, Irvine, CA, 92697, USA. yumayc@uci.edu.
authors.forename: Yumay
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, USA. chiang@uthscsa.edu.
authors.forename: Huai-Chin
authors.initials: HC
authors.lastname: Chiang
authors.affiliation: Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, USA. plitchfield@swisd.net.
authors.forename: Patricia
authors.initials: P
authors.lastname: Litchfield
authors.affiliation: Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, USA. chellexx4090@sbcglobal.net.
authors.forename: Michelle
authors.initials: M
authors.lastname: Pena
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California, Gross Hall 1130, Mail Code, 4086, Irvine, CA, 92697, USA. charityjuang@gmail.com.
authors.forename: Charity
authors.initials: C
authors.lastname: Juang
authors.affiliation: Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, USA. rileyd@uthscsa.edu.|University Transplant Center, The University of Texas Health Science Center at San Antonio, Medicine/Nephrology, MC 7882, 7703 Floyd Curl Dr, San Antonio, TX, 78229-3900, USA. rileyd@uthscsa.edu.|Renal Research Division, South Texas Veterans Health Care System, Audie L. Murphy Division, 7703 Floyd Curl Dr, San Antonio, TX, 78229-3900, USA. rileyd@uthscsa.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Riley
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics*; D003560:Cysts / Q000196:embryology / Q000235:genetics*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D000072380:NIMA-Related Kinase 1; D007690:Polycystic Kidney Diseases / Q000196:embryology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D000072380:NIMA-Related Kinase 1; C000606920:Nek1 protein, mouse; D017346:Protein Serine-Threonine Kinases