Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential of spermatozoa.
GLUT8 is a class 3 sugar transport facilitator which is predominantly expressed in testis and also detected in brain, heart, skeletal muscle, adipose tissue, adrenal gland, and liver. Since its physiological function in these tissues is unknown, we generated a Slc2a8 null mouse and characterized its phenotype. Slc2a8 knockout mice appeared healthy and exhibited normal growth, body weight development and glycemic control, indicating that GLUT8 does not play a significant role for maintenance of whole body glucose homeostasis. However, analysis of the offspring distribution of heterozygous mating indicated a lower number of Slc2a8 knockout offspring (30.5:47.3:22.1%, Slc2a8(+/+), Slc2a8(+/-), and Slc2a8(-/-) mice, respectively) resulting in a deviation (p=0.0024) from the expected Mendelian distribution. This difference was associated with lower ATP levels, a reduced mitochondrial membrane potential and a significant reduction of sperm motility of the Slc2a8 knockout in comparison to wild-type spermatozoa. In contrast, number and survival rate of spermatozoa were not altered. These data indicate that GLUT8 plays an important role in the energy metabolism of sperm cells.
Gawlik
Verena
V
Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
Schmidt
Stefan
S
Scheepers
Andrea
A
Wennemuth
Gunther
G
Augustin
Robert
R
Aumüller
Gerhard
G
Moser
Markus
M
Al-Hasani
Hadi
H
Kluge
Reinhart
R
Joost
Hans-Georg
HG
Schürmann
Annette
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004734:Energy Metabolism; D005260:Female; D018390:Gene Targeting; D051246:Glucose Transport Proteins, Facilitative / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D007150:Immunohistochemistry; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D013081:Sperm Motility / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure
D017931:DNA Primers; D018076:DNA, Complementary; D051246:Glucose Transport Proteins, Facilitative; C498628:Slc2a8 protein, mouse; D000255:Adenosine Triphosphate