Germline deletion of Cetn1 causes infertility in male mice

Abstract

SummaryCentrins 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 2/2 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 2/2 photoreceptor outer segments, and loss of CETN1 had no effect on light-induced translocation of transducin to the inner segment. Although Cetn1 2/2 females and Cetn1 +/2 males had normal fertility, Cetn1 2/2 males were infertile. The Cetn1 2/2 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 2/2 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.

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

“…Although the patient in our study did not have dystonia, she did have manifestations of ADHD with a possible contribution of GNAL loss. Centrins play important roles in the determination of centrosome position and segregation as well as in the process of microtubule severing [Avasthi et al, 2013]. Either deletions or mutations in CETN1 can cause infertility in males but not in females [Hasi-Zogaj et al, 2015].…”

Cell cycle control of spindle pole body duplication and splitting by Sfi1 and Cdc31 in fission yeast

“…Their orthologs play important roles at centrosomes and cilia in a variety of eukaryotes (Avasthi et al, 2013;Azimzadeh et al, 2009;Azimzadeh et al, 2012;Balestra et al, 2013;Dantas et al, 2012;Delaval et al, 2011;Gogendeau et al, 2007;Gogendeau et al, 2008;Jerka-Dziadosz et al, 2013;Stemm-Wolf et al, 2013;Wei et al, 2014;Zhang and He, 2012).…”

Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer

“…90% of the mice injected with MiaPaCa2 cells developed tumors by day 10 post-inoculation. Mice with tumors averaging 50-60 mm 3 were used for imaging and RIT experiments. The radiolabeled antibodies were administered to mice intraperitoneally.…”

“…CETN1 is also a compensatory protein for inactivation of X‐linked CETN2 during spermatogenesis and, in contrast with CETN2, is highly expressed during neonatal development . CETN2 is highly conserved across eukaryotes and is encoded by an X‐linked gene . It is believed to regulate DNA damage recognition during nucleotide excision repair and phosphorylated CETN2 is required for centriole separation during centrosome duplication in cell replication .…”

“…2 CETN2 is highly conserved across eukaryotes and is encoded by an X-linked gene. 3 It is believed to regulate DNA damage recognition during nucleotide excision repair 4 and phosphorylated CETN2 is required for centriole separation during centrosome duplication in cell replication. 4 Sequencing of CETN1 and CETN2 showed approximately 80% homology between the two proteins (Figure1).…”