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PMID:15685642

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Citation

Nayernia, K, Drabent, B, Meinhardt, A, Adham, IM, Schwandt, I, Müller, C, Sancken, U, Kleene, KC and Engel, W (2005) Triple knockouts reveal gene interactions affecting fertility of male mice. Mol. Reprod. Dev. 70:406-16

Abstract

Triple knockout mice were used to investigate the interactions of five genes that were expressed in meiotic and haploid spermatogenic cells in mice, transition protein 2 (Tnp2), proacrosin (Acr), histone H1.1 (H1.1), histone H1t (H1t), and sperm mitochondria-associated cysteine-rich protein (Smcp). TNP2 functions in the replacement of histones and the initial condensation of the spermatid nucleus. The linker histone subtypes H1.1 and H1t are expressed at high levels in meiotic and early haploid cells. ACR, a protease that is stored as a proenzyme in the acrosome, is activated during the acrosome reaction and functions in binding of sperm to the zona pellucida. SMCP is a structural protein in the outer membranes of sperm mitochondria that functions in motility. Previous work demonstrates that homozygous knockout mice lacking each of these proteins individually exhibit no defect in fertility on mixed genetic backgrounds. In contrast, the present study demonstrates that five triple knockout lines, Acr/H1.1/Smcp, Acr/Tnp2/Smcp, Tnp2/H1.1/Smcp, Acr/H1t/Smcp, Tnp2/H1t/Smcp, exhibit drastic reductions in fertility on mixed genetic backgrounds. Analysis of fertility parameters reveal that the decreased fertility is due to line-dependent defects in sperm motility in vitro correlated with reduced migration in the female reproductive tract, and decreased fertilization due to defects in adhesion of sperm to the zona pellucida, the membrane surrounding the egg. It was also found that triple knockout males, that are hemizygous for one locus and homozygous for two other loci, are as subfertile as homozygous triple knockout males, a phenomenon known as haploinsufficiency. These findings demonstrate that male fertility involves synergistic interactions of genes that function in sperm motility and sperm-egg adhesion during fertilization.

Links

PubMed Online version:10.1002/mrd.20227

Keywords

Acrosome Reaction/genetics; Acrosome Reaction/physiology; Animals; Epididymis/cytology; Fertilization/genetics; Fertilization/physiology; Infertility, Male/genetics; Infertility, Male/metabolism; Male; Mice; Mice, Knockout; Sperm Motility/genetics; Sperm Motility/physiology; Spermatozoa/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:STP2

acts_upstream_of_or_within

GO:0030317: flagellated sperm motility

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1888530
MGI:MGI:87884
MGI:MGI:96945

P

Seeded From UniProt

complete

MOUSE:STP2

acts_upstream_of_or_within

GO:0007339: binding of sperm to zona pellucida

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1888530
MGI:MGI:87884
MGI:MGI:96945

P

Seeded From UniProt

complete

MOUSE:MCSP

acts_upstream_of_or_within

GO:0007339: binding of sperm to zona pellucida

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1888530
MGI:MGI:87884
MGI:MGI:98785

P

Seeded From UniProt

complete

MOUSE:ACRO

acts_upstream_of_or_within

GO:0007339: binding of sperm to zona pellucida

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1888530
MGI:MGI:96945
MGI:MGI:98785

P

Seeded From UniProt

complete

MOUSE:ACRO

involved_in

GO:0007338: single fertilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:H1T

acts_upstream_of_or_within

GO:0030317: flagellated sperm motility

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:87884
MGI:MGI:96945
MGI:MGI:98785

P

Seeded From UniProt

complete

MOUSE:H1T

acts_upstream_of_or_within

GO:0007339: binding of sperm to zona pellucida

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:87884
MGI:MGI:96945
MGI:MGI:98785

P

Seeded From UniProt

complete

See also

References

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