title: Impaired somatostatin accumulation within the median eminence in mice with mosaic mutation.
abstract: OBJECTIVE
  The mosaic mutation (Atp7a(mo-ms)) linked to X-chromosome is caused by changes in the Atp7a gene encoding CPx-type protein responsible for the ATP-dependent copper transport across cell membranes. Mosaic mutant males represent an animal model for Menkes disease in humans. Starting from the eighth day of life the mosaic males exhibit a progressive decrease in body weight with poor viability and progressive paresis of the hind limbs. In order to examine whether hypothalamic somatostatin metabolism may be different in normal and copper deficient mice, somatostatin accumulation at the level of median eminence in 14 days old normal and mosaic mutant males was compared.
  
  
  METHODS
  An electron microscopic immunocytochemical study on ultrathin brain slices was performed according to post-embedding immunogold procedure.
  
  
  RESULTS
  In non-mutant animals somatostatin has been detected in many synapses within median eminence. Gold particles moderately decorated synaptic vesicles and mitochondria. In mosaic mutant animals somatostatin expression within the median eminence was very low and only a few gold particles represented somatostatin. Particles were sporadically associated with synaptic vesicles, mitochondria or cytoskeleton elements. Moreover, pre- and post- synaptic parts of synapses were very often swollen.
  
  
  CONCLUSIONS
  Our data demonstrating that copper deficiency leads to the pathological changes within the median eminence ultrastructure and severe impairment of somatostatin expression suggest that this trace metal is an important element necessary for normal neurohormonal brain development.
authors.affiliation: Laboratory of the Cell Ultrastructure, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Wojewodzka
authors.forename: Alina
authors.initials: A
authors.lastname: Gajewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Gajkowska
authors.forename: Jozefa
authors.initials: J
authors.lastname: Styrna
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kochman
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D003300:Copper / Q000172:deficiency*; D000073840:Copper-Transporting ATPases; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008473:Median Eminence / Q000000981:diagnostic imaging / Q000378:metabolism*; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013004:Somatostatin / Q000378:metabolism*; D014463:Ultrasonography; D014960:X Chromosome / Q000235:genetics
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D013004:Somatostatin; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases