Germline deletion of Cetn1 causes infertility in male mice

Abstract

Centrins are calmodulin-like Ca2+-binding proteins that can be found in all ciliated eukaryotic cells from yeast to mammals. Expressed in male germ cells and photoreceptors, centrin 1 (CETN1) resides in the photoreceptor transition zone and connecting cilium. To identify its function in mammals, we deleted Cetn1 by homologous recombination. Cetn1−/− mice were viable and showed no sign of retina degeneration suggesting that CETN1 is nonessential for photoreceptor ciliogenesis or structural maintenance. Phototransduction components localized normally to the Cetn1−/− photoreceptor outer segments, and loss of CETN1 had no effect on light-induced translocation of transducin to the inner segment. Although Cetn1−/− females and Cetn1+/− males had normal fertility, Cetn1−/− males were infertile. The Cetn1−/− testes size was normal, and spermatogonia as well as spermatocytes developed normally. However, spermatids lacked tails suggesting severe spermiogenesis defects at the late maturation phase of spermatozoa. Viable sperm cells were absent and the few surviving spermatozoa were malformed. Light and electron microscopy analyses of Cetn1−/− spermatids revealed failures in centriole rearrangement during basal body maturation and in the basal body-nucleus connection. These results confirm an essential role for CETN1 in late steps of spermiogenesis and spermatid maturation.

Autoren

Prachee Avasthi
Jan Frederik Scheel
Guoxin Ying
Jeanne M Frederick
Wolfgang Baehr
Uwe Wolfrum

DOI

10.1242/jcs.128587

eISSN

1477-9137

ISSN

0021-9533

Zeitschrift

Journal of Cell Science

Sprache

en

Online publication date

2013

Status

Published online

Herausgeber

The Company of Biologists

Herausgeber URL

http://dx.doi.org/10.1242/jcs.128587

Datum der Datenerfassung

2021

Titel

Germline deletion of <i>Cetn1</i> causes infertility in male mice

Data source: Crossref

Abstract

Centrins are calmodulin-like Ca(2+)-binding proteins that can be found in all ciliated eukaryotic cells from yeast to mammals. Expressed in male germ cells and photoreceptors, centrin 1 (CETN1) resides in the photoreceptor transition zone and connecting cilium. To identify its function in mammals, we deleted Cetn1 by homologous recombination. Cetn1(-/-) mice were viable and showed no sign of retina degeneration suggesting that CETN1 is nonessential for photoreceptor ciliogenesis or structural maintenance. Phototransduction components localized normally to the Cetn1(-/-) photoreceptor outer segments, and loss of CETN1 had no effect on light-induced translocation of transducin to the inner segment. Although Cetn1(-/-) females and Cetn1(+/-) males had normal fertility, Cetn1(-/-) males were infertile. The Cetn1(-/-) testes size was normal, and spermatogonia as well as spermatocytes developed normally. However, spermatids lacked tails suggesting severe defects at the late maturation phase of spermiogenesis. Viable sperm cells were absent and the few surviving spermatozoa were malformed. Light and electron microscopy analyses of Cetn1(-/-) spermatids revealed failures in centriole rearrangement during basal body maturation and in the basal-body-nucleus connection. These results confirm an essential role for CETN1 in late steps of spermiogenesis and spermatid maturation.

Addresses

Department of Ophthalmology, University of Utah Health Science Center, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA.

Autoren

Prachee Avasthi
Jan Frederik Scheel
Guoxin Ying
Jeanne M Frederick
Wolfgang Baehr
Uwe Wolfrum

DOI

10.1242/jcs.128587

eISSN

1477-9137

Externe Identifier

PubMed Identifier: 23641067
PubMed Central ID: PMC3711207

Funding acknowledgements

NEI NIH HHS: R01 EY019298
NEI NIH HHS: EY014800-039003
NEI NIH HHS: EY08123
NEI NIH HHS: EY019298
NEI NIH HHS: R01 EY008123
NEI NIH HHS: P30 EY014800

Open access

false

ISSN

0021-9533

Ausgabe der Veröffentlichung

Pt 14

Zeitschrift

Journal of cell science

Schlüsselwörter

Spermatids
Centrioles
Animals
Mice, Inbred C57BL
Mice, Knockout
Mice
Infertility, Male
Transducin
Calcium-Binding Proteins
Chromosomal Proteins, Non-Histone
Cell Cycle
Cell Differentiation
Spermatogenesis
Sequence Deletion
Germ-Line Mutation
Female
Male
Retinal Rod Photoreceptor Cells
Light Signal Transduction

Sprache

eng

Medium

Print-Electronic

Online publication date

2013

Paginierung

3204 - 3213

Datum der Veröffentlichung

2013

Status

Published

Datum der Datenerfassung

2013

Titel

Germline deletion of Cetn1 causes infertility in male mice.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article
Research Support, N.I.H., Extramural

Ausgabe der Zeitschrift

126

Data source: Europe PubMed Central

Abstract

Centrins are calmodulin-like Ca(2+)-binding proteins that can be found in all ciliated eukaryotic cells from yeast to mammals. Expressed in male germ cells and photoreceptors, centrin 1 (CETN1) resides in the photoreceptor transition zone and connecting cilium. To identify its function in mammals, we deleted Cetn1 by homologous recombination. Cetn1(-/-) mice were viable and showed no sign of retina degeneration suggesting that CETN1 is nonessential for photoreceptor ciliogenesis or structural maintenance. Phototransduction components localized normally to the Cetn1(-/-) photoreceptor outer segments, and loss of CETN1 had no effect on light-induced translocation of transducin to the inner segment. Although Cetn1(-/-) females and Cetn1(+/-) males had normal fertility, Cetn1(-/-) males were infertile. The Cetn1(-/-) testes size was normal, and spermatogonia as well as spermatocytes developed normally. However, spermatids lacked tails suggesting severe defects at the late maturation phase of spermiogenesis. Viable sperm cells were absent and the few surviving spermatozoa were malformed. Light and electron microscopy analyses of Cetn1(-/-) spermatids revealed failures in centriole rearrangement during basal body maturation and in the basal-body-nucleus connection. These results confirm an essential role for CETN1 in late steps of spermiogenesis and spermatid maturation.

Autoren

Prachee Avasthi
Jan Frederik Scheel
Guoxin Ying
Jeanne M Frederick
Wolfgang Baehr
Uwe Wolfrum

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/23641067

DOI

10.1242/jcs.128587

eISSN

1477-9137

Externe Identifier

PubMed Central ID: PMC3711207

Funding acknowledgements

NEI NIH HHS: EY08123
NEI NIH HHS: R01 EY019298
NEI NIH HHS: EY014800-039003
NEI NIH HHS: EY019298
NEI NIH HHS: R01 EY008123
NEI NIH HHS: P30 EY014800

Ausgabe der Veröffentlichung

Pt 14

Zeitschrift

J Cell Sci

Schlüsselwörter

CETN1 deletion
Centrin
Flagella
Photoreceptors
Spermatid maturation
Spermiogenesis
Animals
Calcium-Binding Proteins
Cell Cycle
Cell Differentiation
Centrioles
Chromosomal Proteins, Non-Histone
Female
Germ-Line Mutation
Infertility, Male
Light Signal Transduction
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Retinal Rod Photoreceptor Cells
Sequence Deletion
Spermatids
Spermatogenesis
Transducin

Sprache

eng

Country

England

Paginierung

3204 - 3213

PII

jcs.128587

Datum der Veröffentlichung

2013

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

Germline deletion of Cetn1 causes infertility in male mice.

Sub types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

126

Data source: PubMed

Germline deletion of Cetn1 causes infertility in male mice

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