Abstract
We have evaluated the specificity of Cre recombinase activity in transgenic mice expressing Cre under the control of the synatonemal complex protein 1 (Sycp1) gene promoter. Sycp1Cre mice were crossed with the ROSA26 reporter line R26R, to monitor the male germ cell stage-specificity of Cre activity as well as to verify that Cre was not active previously during development of other tissues. X-gal staining detected Cre-mediated recombination only in testis. Detailed histological examination indicated that weak Cre-mediated recombination occurred as early as in zygotene spermatocytes at stage XI of the cycle of the seminiferous epithelium. Robust expression of X-gal was detected in early to mid-late spermatocytes at stages V–VIII. We conclude that this transgenic line is a powerful tool for deleting genes of interest specifically during male meiosis.
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REFERENCES
Ando H, Haruna Y, Miyazaki J, Okabe M and Nakanishi Y (2000) Spermatocyte-specific gene excision by targeted expression of Cre recombinase. Biochem Biophys Res Commun 272: 125–128.
Baudat F, Manova K, Yuen JP, Jasin M and Keeney S (2000) Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol Cell 6: 989–998.
Bergqvist I, Eriksson B, Eriksson M and Holmberg D (1998) Transgenic Cre recombinase expression in germ cells and early embryogenesis directs homogeneous and ubiquitous deletion of loxP-flanked gene segments. FEBS Lett 438: 76–80.
Bhullar B, Schmidt JV, Truong T, Rancourt D and van der Hoorn FA (2001) Germ cell specific promoter drives ectopic transgene expression during embryogenesis. Mol Reprod Dev 59: 25–32.
Dietrich AJ, Kok E, Offenberg HH, Heyting C, de Boer P and Vink AC (1992) The sequential appearance of components of the synaptonemal complex during meiosis of the female rat. Genome 35: 492–497.
Dix DJ, Rosario-Herrle M, Gotoh H, Mori C, Goulding EH et al. (1996) Developmentally regulated expression of Hsp70-2 and a Hsp70-2/lacZ transgene during spermatogenesis. Dev Biol 174: 310–321.
Dobson MJ, Pearlman RE, Karaiskakis A, Spyropoulos B and Moens PB (1994) Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction. J Cell Sci 107: 2749–2760.
Eddy EM (1999) The effects of gene knockouts on spermatogenesis. In: Gagnon C (eds), The Male Gamete: From Basic Science to Clinical Applications. (pp.24–36) Vienna, Illinois: Cache River Press.
Fire A (1992) Histochemical techniques for locating Escherichia coli beta-galactosidase activity in transgenic organisms. Genet Anal Tech Appl 9: 151–158.
Heyting C, Dietrich AJ, Moens PB, Dettmers RJ, Offenberg HH et al. (1989) Synaptonemal complex proteins. Genome 31: 81–87.
Iannello RC, Young J, Sumarsono S, Tymms MJ, Dahl HH et al. (1997) Regulation of Pdha-2 expression is mediated by proximal promoter sequences and CpG methylation. Mol Cell Biol 17: 612–619.
Lallemand Y, Luria V, Haffner-Krausz R and Lonai P (1998) Maternally expressed PGK-Cre transgene as a tool for early and uniform activation of the Cre site-specific recombinase. Transgenic Res. 7: 105–112.
Langford KG, Shai SY, Howard TE, Kovac MJ, Overbeek PA et al. (1991) Transgenic mice demonstrate a testis-specific promoter for angiotensinconverting enzyme. J Biol Chem 266: 15559–15562.
Lomeli H, Ramos-Mejia V, Gertsenstein M, Lobe CG and Nagy A (2000) Targeted insertion of Cre recombinase into the TNAP gene: excision in primordial germ cells. Genesis 26: 116–117.
Meuwissen RL, Offenberg HH, Dietrich AJ, Riesewijk A, van Iersel M et al. (1992) A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes. EMBO J 11: 5091–5100.
Moens PB, Spyropoulos B, Dobson M, Karaiskakis A and Pearlman RE (1992) Searching for synaptonemal complex proteins and their genes. Dev Genet 13: 435–439.
Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26: 99–109.
Offenberg HH, Dietrich AJ and Heyting C (1991) Tissue distribution of two major components of synaptonemal complexes of the rat. Chromosoma 101: 83–91.
O'Gorman S, Dagenais NA, Qian M and Marchuk Y (1997) Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. Proc Natl Acad Sci USA 94: 14602–14607.
Rassoulzadegan M, Magliano M and Cuzin F (2002) Transvection effects involving DNA methylation during meiosis in the mouse. EMBO J 21: 440–450.
Russell LD, Ettlin RA, SinhaHikim AP and Clegg ED (1990) Histological and histopathological evaluation of the testis. Cache River Press, Clearwater, FL.
Sage J, Martin L, Meuwissen R, Heyting C, Cuzin F, et al. (1999) Temporal and spatial control of the Sycp1 gene transcription in the mouse meiosis: regulatory elements active in the male are not sufficient for expression in the female gonad. Mech Dev 80: 29–39.
Schmidt EE, Taylor DS, Prigge JR, Barnett S and Capecchi MR (2000) Illegitimate Credependent chromosome rearrangements in transgenic mouse spermatids. Proc Natl Acad Sci USA 97: 13702–13707.
Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21: 70–71.
Vidal F, Sage J, Cuzin F and Rassoulzadegan M (1998) Cre expression in primary spermatocytes: a tool for genetic engineering of the germ line. Mol Reprod Dev 51: 274–280.
Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG et al. (1997) Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA 94: 3789–3794.
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Chung, S.S.W., Cuzin, F., Rassoulzadegan, M. et al. Primary Spermatocyte-Specific Cre Recombinase Activity in Transgenic Mice. Transgenic Res 13, 289–294 (2004). https://doi.org/10.1023/B:TRAG.0000034716.73957.f7
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DOI: https://doi.org/10.1023/B:TRAG.0000034716.73957.f7