title: Expression of Fraser syndrome genes in normal and polycystic murine kidneys.
abstract: BACKGROUND
  Fraser syndrome (FS) features renal agenesis and cystic kidneys. Mutations of FRAS1 (Fraser syndrome 1)and FREM2 (FRAS1-related extracellular matrix protein 2)cause FS. They code for basement membrane proteins expressed in metanephric epithelia where they mediate epithelial/mesenchymal signalling. Little is known about whether and where these molecules are expressed in more mature kidneys.
  
  
  METHODS
  In healthy and congenital polycystic kidney (cpk)mouse kidneys we sought Frem2 expression using a LacZ reporter gene and quantified Fras family transcripts. Fras1 immunohistochemistry was undertaken in cystic kidneys from cpk mice and PCK (Pkhd1 mutant) rats (models of autosomal recessive polycystic kidney disease) and in wildtype metanephroi rendered cystic by dexamethasone.
  
  
  RESULTS
  Nascent nephrons transiently expressed Frem2 in both tubule and podocyte epithelia. Maturing and adult collecting ducts also expressed Frem2. Frem2 was expressed in cpk cystic epithelia although Frem2 haploinsufficiency did not significantly modify cystogenesis in vivo. Fras1 transcripts were significantly upregulated, and Frem3 downregulated, in polycystic kidneys versus the non-cystic kidneys of littermates. Fras1 was immunodetected in cpk, PCK and dexamethasone-induced cystepithelia.
  
  
  CONCLUSIONS
  These descriptive results are consistent with the hypothesis that Fras family molecules play diverse roles in kidney epithelia. In future, this should be tested by conditional deletion of FS genes in nephron segments and collecting ducts.
authors: UCL Institute of Child Health, London, UK.
authors: Larissa
authors: L
authors: Kerecuk
authors: David A
authors: DA
authors: Long
authors: Zahabia
authors: Z
authors: Ali
authors: Corina
authors: C
authors: Anders
authors: Maria
authors: M
authors: Kolatsi-Joannou
authors: Peter J
authors: PJ
authors: Scambler
authors: Adrian S
authors: AS
authors: Woolf
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D046149:Embryo Culture Techniques; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D058497:Fraser Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007763:Lac Operon; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009399:Nephrons / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: C449819:Cys1 protein, mouse; D016326:Extracellular Matrix Proteins; C482018:Fras1 protein, mouse; C504802:Frem2 protein, mouse; C519661:Frem3 protein, mouse; D008565:Membrane Proteins; C479541:PKHD1 protein, rat; D011956:Receptors, Cell Surface; D003907:Dexamethasone