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.