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Impaired expression of genes coding for reactive oxygen species scavenging enzymes in testes of Mtfr1/Chppr-deficient mice

¹ DOBIG, Universitá di Genova, 16131 Genova, Italy, ² Istituto Nazionale per la Ricerca sul Cancro, Largo R Benzi 10, 16132 Genova, Italy and ³ Dipartimento di Istologia ed Embriologia Medica, Universitá di Roma ‘La Sapienza’, 00161 Rome, Italy

Correspondence should be addressed to P Castagnola; Email: patrizio.castagnola{at}istge.it

Mtfr1/Chppr is a nuclear gene coding for a mitochondrial protein capable of inducing fission of this organelle in a sequence-specific manner. Here we show that in mice, Mtfr1/Chppr is ubiquitously expressed and displays the highest level of expression in pubertal and adult testes and in particular in spermatids and Leydig cells. To investigate Mtfr1 function in vivo, we analyzed homozygous mice null for this gene obtained through a gene trap approach. We show that these mice fail to express Mtfr1 and that in their testes several genes coding for enzymes involved in the defense against oxidative stress are downregulated. Among these, we studied in particular glutathione peroxidase 3 and show its expression in selected testis cell types. Furthermore, we demonstrate oxidative DNA damage specifically in testes of Mtfr1-deficient mice likely resulting from a reduced antioxidant activity. As a whole, these data suggest that Mtfr1 protects the male gonads against oxidative stress.