Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction

Luis Federico Bátiz, Gerardo A. De Blas, Marcela A. Michaut, Alfredo R. Ramírez, Facundo Rodríguez, Marcelo H. Ratto, Cristian Oliver, Claudia N. Tomes, Esteban M. Rodríguez, Luis S. Mayorga

Resultado de la investigación: Article

17 Citas (Scopus)

Resumen

Hydrocephalus with hop gait (hyh) is a recessive inheritable disease that arose spontaneously in a mouse strain. A missense mutation in the Napa gene that results in the substitution of a methionine for isoleucine at position 105 (M105I) of αSNAP has been detected in these animals. αSNAP is a ubiquitous protein that plays a key role in membrane fusion and exocytosis. In this study, we found that male hyh mice with a mild phenotype produced morphologically normal and motile sperm, but had a strongly reduced fertility. When stimulated with progesterone or A23187 (a calcium ionophore), sperm from these animals had a defective acrosome reaction. It has been reported that the M105I mutation affects the expression but not the function of the protein. Consistent with an hypomorphic phenotype, the testes and epididymides of hyh mice had low amounts of the mutated protein. In contrast, sperm had αSNAP levels indistinguishable from those found in wild type cells, suggesting that the mutated protein is not fully functional for acrosomal exocytosis. Corroborating this possibility, addition of recombinant wild type αSNAP rescued exocytosis in streptolysin O-permeabilized sperm, while the mutant protein was ineffective. Moreover, addition of recombinant αSNAP. M105I inhibited acrosomal exocytosis in permeabilized human and wild type mouse sperm. We conclude that the M105I mutation affects the expression and also the function of αSNAP, and that a fully functional αSNAP is necessary for acrosomal exocytosis, a key event in fertilization.

Idioma originalEnglish
Número de artículoe4963
PublicaciónPLoS ONE
Volumen4
N.º3
DOI
EstadoPublished - 23 mar 2009

Huella dactilar

Acrosome Reaction
acrosome reaction
exocytosis
Exocytosis
point mutation
Point Mutation
Spermatozoa
spermatozoa
Defects
mice
Animals
Proteins
proteins
Calcium Ionophores
Isoleucine
Phenotype
Mutant Proteins
mutation
hydrocephalus
phenotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Citar esto

Bátiz, L. F., De Blas, G. A., Michaut, M. A., Ramírez, A. R., Rodríguez, F., Ratto, M. H., ... Mayorga, L. S. (2009). Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction. PLoS ONE, 4(3), [e4963]. https://doi.org/10.1371/journal.pone.0004963
Bátiz, Luis Federico ; De Blas, Gerardo A. ; Michaut, Marcela A. ; Ramírez, Alfredo R. ; Rodríguez, Facundo ; Ratto, Marcelo H. ; Oliver, Cristian ; Tomes, Claudia N. ; Rodríguez, Esteban M. ; Mayorga, Luis S. / Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction. En: PLoS ONE. 2009 ; Vol. 4, N.º 3.
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abstract = "Hydrocephalus with hop gait (hyh) is a recessive inheritable disease that arose spontaneously in a mouse strain. A missense mutation in the Napa gene that results in the substitution of a methionine for isoleucine at position 105 (M105I) of αSNAP has been detected in these animals. αSNAP is a ubiquitous protein that plays a key role in membrane fusion and exocytosis. In this study, we found that male hyh mice with a mild phenotype produced morphologically normal and motile sperm, but had a strongly reduced fertility. When stimulated with progesterone or A23187 (a calcium ionophore), sperm from these animals had a defective acrosome reaction. It has been reported that the M105I mutation affects the expression but not the function of the protein. Consistent with an hypomorphic phenotype, the testes and epididymides of hyh mice had low amounts of the mutated protein. In contrast, sperm had αSNAP levels indistinguishable from those found in wild type cells, suggesting that the mutated protein is not fully functional for acrosomal exocytosis. Corroborating this possibility, addition of recombinant wild type αSNAP rescued exocytosis in streptolysin O-permeabilized sperm, while the mutant protein was ineffective. Moreover, addition of recombinant αSNAP. M105I inhibited acrosomal exocytosis in permeabilized human and wild type mouse sperm. We conclude that the M105I mutation affects the expression and also the function of αSNAP, and that a fully functional αSNAP is necessary for acrosomal exocytosis, a key event in fertilization.",
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Bátiz, LF, De Blas, GA, Michaut, MA, Ramírez, AR, Rodríguez, F, Ratto, MH, Oliver, C, Tomes, CN, Rodríguez, EM & Mayorga, LS 2009, 'Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction', PLoS ONE, vol. 4, n.º 3, e4963. https://doi.org/10.1371/journal.pone.0004963

Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction. / Bátiz, Luis Federico; De Blas, Gerardo A.; Michaut, Marcela A.; Ramírez, Alfredo R.; Rodríguez, Facundo; Ratto, Marcelo H.; Oliver, Cristian; Tomes, Claudia N.; Rodríguez, Esteban M.; Mayorga, Luis S.

En: PLoS ONE, Vol. 4, N.º 3, e4963, 23.03.2009.

Resultado de la investigación: Article

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T1 - Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction

AU - Bátiz, Luis Federico

AU - De Blas, Gerardo A.

AU - Michaut, Marcela A.

AU - Ramírez, Alfredo R.

AU - Rodríguez, Facundo

AU - Ratto, Marcelo H.

AU - Oliver, Cristian

AU - Tomes, Claudia N.

AU - Rodríguez, Esteban M.

AU - Mayorga, Luis S.

PY - 2009/3/23

Y1 - 2009/3/23

N2 - Hydrocephalus with hop gait (hyh) is a recessive inheritable disease that arose spontaneously in a mouse strain. A missense mutation in the Napa gene that results in the substitution of a methionine for isoleucine at position 105 (M105I) of αSNAP has been detected in these animals. αSNAP is a ubiquitous protein that plays a key role in membrane fusion and exocytosis. In this study, we found that male hyh mice with a mild phenotype produced morphologically normal and motile sperm, but had a strongly reduced fertility. When stimulated with progesterone or A23187 (a calcium ionophore), sperm from these animals had a defective acrosome reaction. It has been reported that the M105I mutation affects the expression but not the function of the protein. Consistent with an hypomorphic phenotype, the testes and epididymides of hyh mice had low amounts of the mutated protein. In contrast, sperm had αSNAP levels indistinguishable from those found in wild type cells, suggesting that the mutated protein is not fully functional for acrosomal exocytosis. Corroborating this possibility, addition of recombinant wild type αSNAP rescued exocytosis in streptolysin O-permeabilized sperm, while the mutant protein was ineffective. Moreover, addition of recombinant αSNAP. M105I inhibited acrosomal exocytosis in permeabilized human and wild type mouse sperm. We conclude that the M105I mutation affects the expression and also the function of αSNAP, and that a fully functional αSNAP is necessary for acrosomal exocytosis, a key event in fertilization.

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Bátiz LF, De Blas GA, Michaut MA, Ramírez AR, Rodríguez F, Ratto MH y otros. Sperm from Hyh mice carrying a point mutation in αSNAP have a defect in acrosome reaction. PLoS ONE. 2009 mar 23;4(3). e4963. https://doi.org/10.1371/journal.pone.0004963