Document Detail


Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem cells.
MedLine Citation:
PMID:  8522326     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lesch-Nyhan syndrome is caused by a severe genetic deficiency of hypoxanthine phosphoribosyltransferase (HPRT) and is characterized by central nervous system disorders, gout, and in some cases, macrocytic anemia. Women heterozygous for HPRT deficiency are healthy but their somatic cells are mosaic for enzyme deficiency owing to random inactivation of the X chromosome. Frequencies of red blood cells and T cells deficient in HPRT are significantly lower than the expected 50% in heterozygotes, suggesting that HPRT-negative blood cells are selected against in heterozygotes. To determine at which stage of hematopoiesis such selection occurs, we determined the frequencies of HPRT-negative T, B and erythroid precursor cells in three heterozygotes. Since the cloning efficiencies of T and B cells and colony forming efficiency of burst-forming unit erythroid (BFU-E) for sample from Lesch-Nyhan patients were similar to those of normal cells, HPRT deficiency does not seem to render the differentiated cells less efficient for proliferation. However, the frequencies of HPRT-negative T and B cells, and BFU-E were all less than 10% in each of the three heterozygotes. Although the frequencies of HPRT-negative cells showed tenfold variations between the heterozygotes, each heterozygote had similar frequencies of HPRT-negative cells in the three cell types. These results suggest that HPRT is important at early stages of hematopoiesis, but less so after the cells have differentiated into T cells, B cells and erythroid precursor cells.
Authors:
M Hakoda; Y Hirai; M Akiyama; H Yamanaka; C Terai; N Kamatani; S Kashiwazaki
Related Documents :
6152956 - The effects of diagnostic ultrasonography on the frequencies of sister chromatid exchan...
15850426 - Monitoring cell survival after extraction of a single subcellular organelle using optic...
7907116 - Nuclear scaffold organization in the x-ray sensitive chinese hamster mutant cell line, ...
3778446 - Fusion of mammalian cells in culture is obtained by creating the contact between cells ...
2983006 - Effect of heat shock on epstein-barr virus and cytomegalovirus expression.
9144086 - Decreased phosphatidylcholine biosynthesis and abnormal distribution of ctp:phosphochol...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human genetics     Volume:  96     ISSN:  0340-6717     ISO Abbreviation:  Hum. Genet.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-01-22     Completed Date:  1996-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  674-80     Citation Subset:  IM    
Affiliation:
Institute of Rheumatology, Tokyo Women's Medical College, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
B-Lymphocytes / enzymology
Cell Line
Clone Cells
Erythrocytes / enzymology
Female
Hematopoiesis
Hematopoietic Stem Cells / enzymology*
Heterozygote*
Heterozygote Detection
Humans
Hypoxanthine Phosphoribosyltransferase / blood*,  deficiency*,  genetics
Lesch-Nyhan Syndrome / blood,  enzymology*,  genetics*
Organ Specificity
T-Lymphocytes / enzymology
Thioguanine / pharmacology
X Chromosome*
Chemical
Reg. No./Substance:
154-42-7/Thioguanine; EC 2.4.2.8/Hypoxanthine Phosphoribosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5.
Next Document:  Chromosome 17 abnormalities and lack of TP53 mutations in paediatric central nervous system tumours.