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Transgenic Rodent Assay for Quantifying Male Germ Cell Mutant Frequency
Published on: August 6, 2014
Mutagenesis-generated mouse models of human infertility with abnormal sperm
C Lessard1, H Lothrop, J C Schimenti
1The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Human Reproduction (Oxford, England)
|August 22, 2006
Summary
Ethylnitrosourea (ENU) mutagenesis identified three new genes causing male infertility in mice. These mutations result in low sperm count, poor motility, and abnormal morphology, aiding the study of human oligoasthenoteratozoospermia.
Area of Science:
- Genetics
- Reproductive Biology
- Developmental Biology
Background:
- Understanding the causes of human male infertility, characterized by low sperm count, motility, and morphology (oligoasthenoteratozoospermia), is challenging due to a lack of suitable animal models.
- Animal models are crucial for dissecting the genetic and molecular underpinnings of complex reproductive disorders.
Purpose of the Study:
- To identify novel genetic factors contributing to male infertility using a forward genetics approach in mice.
- To characterize the phenotype and genetic location of newly discovered mutations causing oligoasthenoteratozoospermia.
Main Methods:
- Utilized ethylnitrosourea (ENU) mutagenesis to induce heritable mutations in mice.
- Phenotypically characterized mutant male mice for sperm count, motility, and morphology.
- Conducted in vitro fertilization assays and ultrastructural analyses of sperm.
- Performed genetic mapping to determine the chromosomal location of identified mutations.
Main Results:
- Identified three independent ENU-induced mutations (swm2, repro2, repro3) causing oligoasthenoteratozoospermia in male mice.
- Mutant males exhibited significantly reduced sperm concentration, poor sperm morphology, and negligible motility.
- Ultrastructural examination revealed diverse sperm abnormalities in both testicular and epididymal sperm.
- Genetic mapping localized swm2 to chromosome 7, repro2 to chromosome 5, and repro3 to chromosome 10.
Conclusions:
- Single-gene mutations can lead to complex, non-specific sperm pathologies, offering insights into human male infertility management.
- Identification of these mutated loci will advance the understanding of the etiology of complex infertility syndromes with sperm abnormalities.
- These mouse models provide valuable tools for studying the genetic basis of oligoasthenoteratozoospermia.
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