Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse

Human Molecular Genetics
Junko MatsudaYasuhiro Kuroda

Abstract

The sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins that are encoded by a single gene in tandem within a large precursor protein (prosaposin) and are required for in vivo degradation of some sphingolipids with relatively short carbohydrate chains. Human patients with prosaposin or specific saposin B or C deficiency are known, and prosaposin- and saposin A-deficient mouse lines have been generated. Experimental evidence suggests that saposin D may be a lysosomal acid ceramidase activator. However, no specific saposin D deficiency state is known in any mammalian species. We have generated a specific saposin D(-/-) mouse by introducing a mutation (C509S) into the saposin D domain of the mouse prosaposin gene. Saposin D(-/-) mice developed progressive polyuria at around 2 months and ataxia at around 4 months. Pathologically, the kidney of saposin D(-/-) mice showed renal tubular degeneration and eventual hydronephrosis. In the nervous system, progressive and selective loss of the cerebellar Purkinje cells in a striped pattern was conspicuous, and almost all Purkinje cells disappeared by 12 months. Biochemically, ceramides, particularly those containing hydroxy fatty acids accumulated in t...Continue Reading

References

May 15, 1992·Biochemical and Biophysical Research Communications·M TsudaT Kitagawa
Oct 1, 1970·Chemistry and Physics of Lipids·K A Karlsson
Jun 1, 1971·Scandinavian Journal of Clinical and Laboratory Investigation·K Samuelsson, R Zetterström
May 5, 1970·Biochimica Et Biophysica Acta·J B Hey, G M Gray
May 16, 1994·Biochemical and Biophysical Research Communications·A KleinK Sandhoff
Jun 1, 1994·Archives of Biochemistry and Biophysics·N AzumaY Kishimoto
Jan 1, 1993·Acta Neuropathologica·Y HigashiK Suzuki
Mar 19, 1993·Science·L M ObeidY A Hannun
Jul 19, 1996·The Journal of Biological Chemistry·T LeonovaG A Grabowski
Sep 15, 1998·Trends in Neurosciences·J Voogd, M Glickstein
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y WangD Givol
Jun 16, 2001·American Journal of Physiology. Renal Physiology·R K MalikR L Chevalier
Jun 15, 2001·The Journal of Biological Chemistry·F CiaffoniA M Vaccaro
Feb 22, 2002·The Journal of Biological Chemistry·Stephane LefrancoisCarlos R Morales
Sep 5, 2002·Molecular Genetics and Metabolism·Ying SunGregory A Grabowski
Sep 10, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Shoji KagamiYasuhiro Kuroda
Jan 16, 2003·The Journal of Comparative Neurology·Justyna R SarnaRichard Hawkes
May 8, 2003·The Biochemical Journal·Fiorella CiaffoniAnna Maria Vaccaro
Oct 22, 2003·Progress in Neurobiology·Justyna R Sarna, Richard Hawkes
Dec 23, 2003·The Journal of Comparative Neurology·Nobuo TeradaShinichi Ohno
Jan 13, 2004·Nature Immunology·Suk-Jo Kang, Peter Cresswell
Jan 13, 2004·Nature Immunology·Florian WinauUlrich E Schaible

❮ Previous
Next ❯

Citations

May 14, 2011·DNA and Cell Biology·Meixia FangXiquan Zhang
May 16, 2008·Human Molecular Genetics·Ying SunGregory A Grabowski
Dec 18, 2009·Human Molecular Genetics·Ying SunGregory A Grabowski
Dec 2, 2011·Journal of Biochemistry·Kousaku Ohno
Apr 20, 2011·Cold Spring Harbor Perspectives in Biology·Heike Schulze, Konrad Sandhoff
Mar 10, 2010·Journal of Lipid Research·You-Hai XuGregory A Grabowski
Nov 21, 2007·Biological Chemistry·Heike SchulzeKonrad Sandhoff
Nov 13, 2009·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Azusa YoneshigeJunko Matsuda
Dec 12, 2012·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Konrad Sandhoff
Mar 1, 2013·Human Molecular Genetics·Ying SunGregory A Grabowski
Aug 31, 2006·Proceedings of the National Academy of Sciences of the United States of America·S Joshua LangmadeDaniel S Ory
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Weiming YuanPeter Cresswell
Aug 24, 2010·Neuromolecular Medicine·Matthias Eckhardt
Oct 20, 2009·FEBS Letters·Thomas Kolter, Konrad Sandhoff
Jul 23, 2015·The Laryngoscope·Lawrence R LustigOmar Akil
Dec 23, 2009·Biochimica Et Biophysica Acta·Hiroko Hama
Jan 21, 2015·Biochemical and Biophysical Research Communications·James M GruschusJennifer C Lee
Feb 26, 2008·Biochimica Et Biophysica Acta·Frédérique SabourdyThierry Levade
Feb 11, 2015·Biochimica Et Biophysica Acta·Frédérique SabourdyThierry Levade
Mar 19, 2008·Biochimica Et Biophysica Acta·Rosa SalvioliAnna Maria Vaccaro
Jul 21, 2006·Biochimica Et Biophysica Acta·Thomas Kolter, Konrad Sandhoff
Aug 19, 2014·Brain Research·Rebecca C MeyerRandy A Hall
Nov 7, 2006·Biochimica Et Biophysica Acta·Elena I Posse de Chaves
Oct 19, 2005·The Journal of Biological Chemistry·Thomas KolterKonrad Sandhoff
Jan 12, 2019·Journal of Molecular Neuroscience : MN·Miriam KolnikovaJan Chandoga
Mar 24, 2020·Brain : a Journal of Neurology·Yutaka OjiNobutaka Hattori
Oct 3, 2018·Aging and Disease·Stefanie HardtIrmgard Tegeder
Jul 1, 2020·Frontiers in Neuroscience·Tina LoefflerBirgit Hutter-Paier
Jul 27, 2012·American Journal of Physiology. Renal Physiology·Harumi HisakiTomoki Okazaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.