Absence of the prion protein homologue Doppel causes male sterility.
The agent that causes prion diseases is thought to be identical with PrP(Sc), a conformer of the normal prion protein PrP(C). PrP(C)-deficient mice do not exhibit major pathologies, perhaps because they express a protein termed Dpl, which shares significant biochemical and structural homology with PrP(C). To investigate the physiological function of Dpl, we generated mice harbouring a homozygous disruption of the Prnd gene that encodes Dpl. Dpl deficiency did not interfere with embryonic and postnatal development, but resulted in male sterility. Dpl protein was expressed at late stages of spermiogenesis, and spermatids of Dpl mutants were reduced in numbers, immobile, malformed and unable to fertilize oocytes in vitro. Mechanical dissection of the zona pellucida partially restored in vitro fertilization. We conclude that Dpl regulates male fertility by controlling several aspects of male gametogenesis and sperm-egg interaction.
Institute of Neuropathology, UniversitätsSpital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.
Axel
A
Behrens
Nicolas
N
Genoud
Heike
H
Naumann
Thomas
T
Rülicke
Fredi
F
Janett
Frank L
FL
Heppner
Birgit
B
Ledermann
Adriano
A
Aguzzi
D000818:Animals; D002469:Cell Separation; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006720:Homozygote; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011328:Prions / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000254:growth & development
D058851:GPI-Linked Proteins; D011328:Prions; C122036:Prnd protein, mouse