Document Detail


Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.
MedLine Citation:
PMID:  9593760     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic disorder characterized by mental retardation, congenital cataracts, and renal tubular dysfunction. The Lowe syndrome gene, OCRL1, encodes a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex. The pathogenesis of Lowe syndrome due to deficiency of a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex is unknown. We have used targeted disruption in embryonic stem cells to make mice deficient in Ocrl1, the mouse homologue for OCRL1, as an animal model for the disease. Surprisingly, mice deficient in Ocrl1 do not develop the congenital cataracts, renal Fanconi syndrome, or neurological abnormalities seen in the human disorder. We hypothesized that Ocrl1 deficiency is complemented in mice by inositol polyphosphate 5-phosphatase (Inpp5b), an autosomal gene that encodes a phosphatidylinositol bisphosphate 5-phosphatase highly homologous to Ocrl1. We created mice deficient in Inpp5b; the mice were viable and fertile without phenotype except for testicular degeneration in males beginning after sexual maturation. We crossed mice deficient in Ocrl1 to mice deficient in Inpp5b. No liveborn mice or embryos lacking both enzymes were found, demonstrating that Ocrl1 and Inpp5b have overlapping functions in mice and suggesting that the lack of phenotype in Ocrl1-deficient mice may be due to compensating Inpp5b function.
Authors:
P A Jänne; S F Suchy; D Bernard; M MacDonald; J Crawley; A Grinberg; A Wynshaw-Boris; H Westphal; R L Nussbaum
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  101     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-19     Completed Date:  1998-06-19     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2042-53     Citation Subset:  AIM; IM    
Affiliation:
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19102, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amino Acids / urine
Animals
Crosses, Genetic
Disease Models, Animal
Gene Expression / genetics
Gene Targeting
Humans
Mice
Mice, Knockout
Molecular Sequence Data
Motor Activity / physiology
Oculocerebrorenal Syndrome / genetics*,  physiopathology
Phenotype
Phosphoric Monoester Hydrolases / genetics*,  physiology
Proteins / genetics*,  physiology
RNA Splicing
RNA, Messenger / metabolism
Stem Cells
Grant Support
ID/Acronym/Agency:
R01-HD-23245/HD/NICHD NIH HHS; T32-GM-07170/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Ocrl protein, mouse; 0/Proteins; 0/RNA, Messenger; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.36/OCRL protein, human; EC 3.1.3.36/phosphoinositide 5-phosphatase; EC 3.1.3.56/inositol-1,4,5-trisphosphate 5-phosphatase
Comments/Corrections

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