Mol. Hum. Reprod. Advance Access originally published online on January 18, 2006
Molecular Human Reproduction 2005 11(12):871-880; doi:10.1093/molehr/gah251
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A repository of ENU mutant mouse lines and their potential for male fertility research
1Centre for Molecular Reproduction and Development, Monash Institute of Medical Research, 2ARC Centre of Excellence in Biotechnology and Development, Monash University, Melbourne and 3The Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australia
4 To whom correspondence should be addressed at: The ARC Centre of Excellence in Biotechnology and Development, The Centre for Molecular Reproduction and Development, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton 3168, Australia. E-mail: moira.obryan{at}med.monash.edu.au
Many of the proteins and their encoding genes involved in spermatogenesis are unknown, making the specific diagnosis and treatment of infertility in males difficult and highlighting the importance of identifying new genes that are involved in spermatogenesis. Through genome-wide chemical mutagenesis using N-ethyl-N-nitrosourea (ENU) and a three-generation breeding scheme to isolate recessive mutations, we have identified mouse lines with a range of abnormalities relevant to human male fertility. Abnormal phenotypes included hypospermatogenesis, Sertoli cell-only (SCO) seminiferous tubules, germ-cell arrest and abnormal spermiogenesis and were accompanied, in some, with abnormal serum levels of reproductive hormones. In total, from 65 mouse lines, 14 showed a reproductive phenotype consistent with a recessive mutation. This study shows that it is feasible to use ENU mutagenesis as an effective and rapid means of generating mouse models relevant to furthering our understanding of human male infertility. Spermatozoa and genomic DNA from all mouse lines, including those with abnormal reproductive tract parameters, have been cryopreserved for the regeneration of lines as required. This repository will form a valuable resource for the identification and analysis of key regulators of multiple aspects of male fertility.
Key words: FSH/infertility/inhibin/sperm/testis
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