title: Transketolase haploinsufficiency reduces adipose tissue and female fertility in mice.
abstract: 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.
authors.affiliation: Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730, USA.
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Xu
authors.forename: Eric F
authors.initials: EF
authors.lastname: Wawrousek
authors.forename: Joram
authors.initials: J
authors.lastname: Piatigorsky
mesh_terms: 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*
chemical_list: D005136:Eye Proteins; D020738:Leptin; D013006:Growth Hormone; D014174:Transketolase