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 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.


CONCLUSIONS
The impaired gametogenesis of homozygous males and females can explain their infertility.
Winterhager
Elke
E
Institut für Anatomie, Universität Duisburg-Essen, 45122 Essen, Germany. elke.winterhager@uk-essen.de <elke.winterhager@uk-essen.de>
Pielensticker
Nicole
N
Freyer
Jennifer
J
Ghanem
Alexander
A
Schrickel
Jan W
JW
Kim
Jung-Sun
JS
Behr
Rüdiger
R
Grümmer
Ruth
R
Maass
Karen
K
Urschel
Stephanie
S
Lewalter
Thorsten
T
Tiemann
Klaus
K
Simoni
Manuela
M
Willecke
Klaus
K
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D000072259:Connexin 26; D018031:Connexin 43 / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D004562:Electrocardiography; D053595:Embryonic Stem Cells; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010053:Ovary / Q000503:physiopathology*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000503:physiopathology*; D014162:Transfection
D018031:Connexin 43; D017630:Connexins; D000072259:Connexin 26