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The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice

Vallet-Erdtmann, V; Tavernier, G; Contreras, Juan Antonio LU ; Mairal, A; Rieu, C; Touzalin, AM; Holm, Cecilia LU ; Jegou, B and Langin, D (2004) In Journal of Biological Chemistry 279(41). p.42875-42880
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 non-gonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity... (More)
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 non-gonadal 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
41
pages
42875 - 42880
publisher
ASBMB
external identifiers
  • wos:000224226400065
  • scopus:5644254359
ISSN
1083-351X
DOI
10.1074/jbc.M403495200
language
English
LU publication?
yes
id
9598bbf3-7a9b-4360-b2e6-0c645ce849b1 (old id 266363)
date added to LUP
2007-11-04 08:06:39
date last changed
2017-01-01 05:18:10
@article{9598bbf3-7a9b-4360-b2e6-0c645ce849b1,
  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 non-gonadal 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.},
  author       = {Vallet-Erdtmann, V and Tavernier, G and Contreras, Juan Antonio and Mairal, A and Rieu, C and Touzalin, AM and Holm, Cecilia and Jegou, B and Langin, D},
  issn         = {1083-351X},
  language     = {eng},
  number       = {41},
  pages        = {42875--42880},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice},
  url          = {http://dx.doi.org/10.1074/jbc.M403495200},
  volume       = {279},
  year         = {2004},
}