Transketolase haploinsufficiency reduces adipose tissue and female fertility in mice.
Transketolase (TKT) is a ubiquitous enzyme used in multiple metabolic pathways. We show here by gene targeting that TKT-null mouse embryos are not viable and that disruption of one TKT allele can cause growth retardation ( approximately 35%) and preferential reduction of adipose tissue ( approximately 77%). Other TKT(+/-) tissues had moderate ( approximately 33%; liver, gonads) or relatively little ( approximately 7 to 18%; eye, kidney, heart, brain) reductions in mass. These mice expressed a normal level of growth hormone and reduced leptin levels. No phenotype was observed in the TKT(+/-) cornea, where TKT is especially abundant in wild-type mice. The small female TKT(+/-) mice mated infrequently and had few progeny (with a male/female ratio of 1.4:1) when pregnant. Thus, TKT in normal mice appears to be carefully balanced at a threshold level for well-being. Our data suggest that TKT deficiency may have clinical significance in humans and raise the possibility that obesity may be treated by partial inhibition of TKT in adipose tissue.
Xu
Zheng-Ping
ZP
Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730, USA.
Wawrousek
Eric F
EF
Piatigorsky
Joram
J
D000273:Adipose Tissue / Q000201:enzymology / Q000473:pathology*; D000483:Alleles; D000818:Animals; D001835:Body Weight; D003315:Cornea / Q000201:enzymology; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D018390:Gene Targeting; D006130:Growth Disorders / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013006:Growth Hormone / Q000097:blood; D006579:Heterozygote; D007247:Infertility, Female / Q000201:enzymology / Q000235:genetics*; D007438:Introns / Q000235:genetics; D020738:Leptin / Q000172:deficiency; D008098:Litter Size / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009028:Morula / Q000473:pathology; D016254:Mutagenesis, Insertional; D009929:Organ Size; D010641:Phenotype; D011247:Pregnancy; D012726:Sexual Behavior, Animal; D014174:Transketolase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D005136:Eye Proteins; D020738:Leptin; D013006:Growth Hormone; D014174:Transketolase