Cargando…

Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart

BACKGROUND: In order to further distinguish unique from general functions of connexin43, we have generated mice in which the coding region of connexin43 was replaced by that of connexin26. RESULTS: Heterozygous mothers showed impaired mammary gland development responsible for decreased lactation and...

Descripción completa

Detalles Bibliográficos
Autores principales: Winterhager, Elke, Pielensticker, Nicole, Freyer, Jennifer, Ghanem, Alexander, Schrickel, Jan W, Kim, Jung-Sun, Behr, Rüdiger, Grümmer, Ruth, Maass, Karen, Urschel, Stephanie, Lewalter, Thorsten, Tiemann, Klaus, Simoni, Manuela, Willecke, Klaus
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852306/
https://www.ncbi.nlm.nih.gov/pubmed/17408477
http://dx.doi.org/10.1186/1471-213X-7-26
_version_ 1782133032289828864
author Winterhager, Elke
Pielensticker, Nicole
Freyer, Jennifer
Ghanem, Alexander
Schrickel, Jan W
Kim, Jung-Sun
Behr, Rüdiger
Grümmer, Ruth
Maass, Karen
Urschel, Stephanie
Lewalter, Thorsten
Tiemann, Klaus
Simoni, Manuela
Willecke, Klaus
author_facet Winterhager, Elke
Pielensticker, Nicole
Freyer, Jennifer
Ghanem, Alexander
Schrickel, Jan W
Kim, Jung-Sun
Behr, Rüdiger
Grümmer, Ruth
Maass, Karen
Urschel, Stephanie
Lewalter, Thorsten
Tiemann, Klaus
Simoni, Manuela
Willecke, Klaus
author_sort Winterhager, Elke
collection PubMed
description BACKGROUND: In order to further distinguish unique from general functions of connexin43, we have generated mice in which the coding region of connexin43 was replaced by that of connexin26. RESULTS: Heterozygous mothers showed impaired mammary gland development responsible for decreased lactation and early postnatal death of the pups which could be partially rescued by wild type foster mothers. Only about 17% of the homozygous connexin43 knock-in connexin26 mice instead of 25% expected according to Mendelian inheritance, were born and only 6% survived to day 21 post partum and longer. Neonatal and adult connexin43 knock-in connexin26 mice exhibited slowed ventricular conduction in their hearts, i.e. similar but delayed electrophysiological abnormalities as connexin43 deficient mice. Furthermore, connexin43 knock-in connexin26 male and female mice were infertile and exhibited hypotrophic gonads. In testes, tubuli seminiferi were developed and spermatogonia as well as some primary spermatocytes were present, but further differentiated stages of spermatogenesis were absent. Ovaries of female connexin43 knock-in connexin26 mice revealed only few follicles and the maturation of follicles was completely impaired. CONCLUSION: The impaired gametogenesis of homozygous males and females can explain their infertility.
format Text
id pubmed-1852306
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-18523062007-04-17 Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart Winterhager, Elke Pielensticker, Nicole Freyer, Jennifer Ghanem, Alexander Schrickel, Jan W Kim, Jung-Sun Behr, Rüdiger Grümmer, Ruth Maass, Karen Urschel, Stephanie Lewalter, Thorsten Tiemann, Klaus Simoni, Manuela Willecke, Klaus BMC Dev Biol Research Article BACKGROUND: In order to further distinguish unique from general functions of connexin43, we have generated mice in which the coding region of connexin43 was replaced by that of connexin26. RESULTS: Heterozygous mothers showed impaired mammary gland development responsible for decreased lactation and early postnatal death of the pups which could be partially rescued by wild type foster mothers. Only about 17% of the homozygous connexin43 knock-in connexin26 mice instead of 25% expected according to Mendelian inheritance, were born and only 6% survived to day 21 post partum and longer. Neonatal and adult connexin43 knock-in connexin26 mice exhibited slowed ventricular conduction in their hearts, i.e. similar but delayed electrophysiological abnormalities as connexin43 deficient mice. Furthermore, connexin43 knock-in connexin26 male and female mice were infertile and exhibited hypotrophic gonads. In testes, tubuli seminiferi were developed and spermatogonia as well as some primary spermatocytes were present, but further differentiated stages of spermatogenesis were absent. Ovaries of female connexin43 knock-in connexin26 mice revealed only few follicles and the maturation of follicles was completely impaired. CONCLUSION: The impaired gametogenesis of homozygous males and females can explain their infertility. BioMed Central 2007-04-04 /pmc/articles/PMC1852306/ /pubmed/17408477 http://dx.doi.org/10.1186/1471-213X-7-26 Text en Copyright © 2007 Winterhager et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Winterhager, Elke
Pielensticker, Nicole
Freyer, Jennifer
Ghanem, Alexander
Schrickel, Jan W
Kim, Jung-Sun
Behr, Rüdiger
Grümmer, Ruth
Maass, Karen
Urschel, Stephanie
Lewalter, Thorsten
Tiemann, Klaus
Simoni, Manuela
Willecke, Klaus
Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
title Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
title_full Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
title_fullStr Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
title_full_unstemmed Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
title_short Replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
title_sort replacement of connexin43 by connexin26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852306/
https://www.ncbi.nlm.nih.gov/pubmed/17408477
http://dx.doi.org/10.1186/1471-213X-7-26
work_keys_str_mv AT winterhagerelke replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT pielenstickernicole replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT freyerjennifer replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT ghanemalexander replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT schrickeljanw replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT kimjungsun replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT behrrudiger replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT grummerruth replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT maasskaren replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT urschelstephanie replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT lewalterthorsten replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT tiemannklaus replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT simonimanuela replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart
AT willeckeklaus replacementofconnexin43byconnexin26intransgenicmiceleadstodysfunctionalreproductiveorgansandslowedventricularconductionintheheart