Title of article :
Male infertility and thiamine-dependent erythroid hypoplasia in mice lacking thiamine transporter Slc19a2
Author/Authors :
Yao، David D. نويسنده , , Fleming، Judith C. نويسنده , , Tartaglini، Elena نويسنده , , Kawatsuji، Ryosuke نويسنده , , Fujiwara,، Yuko نويسنده , , Bednarski، Jeffrey J. نويسنده , , Fleming، Mark D. نويسنده , , Neufeld، Ellis J. نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2003
Pages :
-233
From page :
234
To page :
0
Abstract :
Thiamine-responsive megaloblastic anemia with diabetes and deafness (TRMA) is an autosomal recessive disease caused by mutations in the high-affinity thiamine transporter gene SLC19A2. To study the role of thiamine transport in the pathophysiology of TRMA syndrome and of each of the component disorders, we created a targeted disruption of the Slc19a2 gene in mice. Slc19a2 -/mice are viable and females are fertile. Male -/- mice on a pure 129/Sv background are infertile with small testes (testis/body WEIGHT=0.13 +- 0.04 knockout vs. 0.35 +-0.05 wild type, P<0.000005). The lack of developing germ cells beyond primary spermatocytes suggests an arrest in spermatogenesis prior to meiosis II. Nuclear chromatin changes indicative of apoptosis are present. No mature sperm are found in the tubules or epididymis. This phenotype suggests a previously unknown role for thiamine transport in spermatogenesis and male fertility. Slc19a2 -/mice on a pure 129/Sv background develop reticulocytopenia after two weeks on thiaminedepleted chow with a virtual absence of reticulocytes in the peripheral blood (0.12% knockout vs. 2.58% wild type, P=0.0079). Few erythroid precursors are found in the bone marrow. Contrary to human TRMA syndrome, we see no evidence of megaloblastosis or ringed sideroblasts in the bone marrow of Slc19a2 -/- mice in thiamine-replete or thiamine-deficient dietary states. Phenotypic differences between TRMA patients and Slc19a2-/- mice might be explained by dissimilar tissue expression patterns of the transporter, as well as by differing metabolic needs and possible different species-specific contributions of the related thiamine transporter Slc19a3.
Keywords :
Reticulocytopenia , TRMA , Erythroid hypoplasia , Slc19a2 , Vitamin B1 , Thiamine transport , spermatogenesis
Journal title :
MOLECULAR GENETICS AND METABOLISM
Serial Year :
2003
Journal title :
MOLECULAR GENETICS AND METABOLISM
Record number :
87392
Link To Document :
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