Author/Editor     Vallet-Erdtmann, Virginie; Tavernier, Genevieve; Contreras, Juan Antonio; Mairal, Aline; Rieu, Cécile; Touzalin, Anne-Marie; Holm, Cecilia; Jegou, Bernard; Langin, Dominique
Title     The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice
Type     članek
Source     J Biol Chem
Vol. and No.     Letnik 279, št. 41
Publication year     2004
Volume     str. 42875-80
Language     eng
Abstract     Inactivation of the hormone-sensitive lipase gene (HSL) confers male sterility with a major defect in spermatogenesis. Several forms of HSL are expressed in testis. HSLtes mRNA and protein are found in early and elongated spermatids, respectively. The other forms are expressed in diploid germ cells and interstitial cells of the testis. To determine whether the absence of the testis-specific form of HSL, HSLtes, was responsible for the infertility in HSL-null mice, we generated transgenic mice expressing HSLtes under the control of its own promoter. The transgenic animals were crossed with HSL-null mice to produce mice deficient in HSL in nongonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity was almost completely blunted in HSL-deficient testis. Mice with one allele of the transgene showed an increase in enzymatic activity and a small elevation in the production of spermatozoa. The few fertile hemizygous male mice produced litters of very small to small size. The presence of the two alleles led to a doubling in cholesteryl ester hydrolase activity, which represented 25% of the wild type values associated with a qualitatively normal spermatogenesis and a partial restoration of sperm reserves. The fertility of these mice was totally restored with normal litter sizes. In line with the importance of the esterase activity, HSLtes transgene expression reversed the cholesteryl ester accumulation observed in HSL-null mice. Therefore, expression of HSLtes and cognate cholesteryl ester hydrolase activity leads to a rescue of the infertility observed in HSL-deficient male mice.
Descriptors     ALLELES
BLOTTING, WESTERN
BODY WEIGHT
CHOLESTEROL ESTERASE
CHROMATOGRAPHY, GAS
CROSSES, GENETIC
EPIDIDYMIS
GENOTYPE
GERM CELLS
HOMOZYGOTE
INFERTILITY, MALE
MICE
MICE, TRANSGENIC
RNA, MESSENGER
SPERMATOZOA
TESTIS
TISSUE DISTRIBUTION
TRANSGENES