Mouse spermatozoa with higher fertilization rates have thinner nuclei

Mashiko D, Ikawa M, Fujimoto K. 2017. Mouse spermatozoa with higher fertilization rates have thinner nuclei. PeerJ 5:e3913 https://doi.org/10.7717/peerj.391

Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA

Mashiko, D., Fujihara, Y., Satouh, Y. et al. Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA. Sci Rep 3, 3355 (2013). https://doi.org/10.1038/srep0335

The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction

Ca2+ influx triggers sperm capacitation; however, the underlying regulatory mechanisms remain incompletely understood. Here, we show that CNNM4, a Mg2+ transporter, is required for Ca2+ influx during capacitation. We find that Cnnm4-deficient male mice are almost infertile because of sperm dysfunction. Motion analyses show that hyperactivation, a qualitative change in the mode of sperm motility during capacitation, is abrogated in Cnnm4-deficient sperm. In contrast, tyrosine phosphorylation of flagellar proteins, a hallmark of capacitation, is excessively augmented. These seemingly paradoxical phenotypes of Cnnm4-deficient sperm are very similar to those of sperm lacking a functional cation channel of sperm (CatSper) channel, which plays an essential role in Ca2+ influx during sperm capacitation. Ca2+ imaging analyses demonstrate that Ca2+ influx is perturbed in Cnnm4-deficient sperm, and forced Ca2+ entry into these sperm normalizes the level of tyrosine phosphorylation. Furthermore, we confirm the importance of CNNM4 in sperm by generating germcell- specific Cnnm4-deficient mice. These results suggest a new role of CNNM4 in sperm Ca2+ homeostasis

Gene-deficient mouse model established by CRISPR/Cas9 system reveals 15 reproductive organ-enriched genes dispensable for male fertility

Since the advent of gene-targeting technology in embryonic stem cells, mice have become a primary model organism for investigating human gene function due to the striking genomic similarities between the two species. With the introduction of the CRISPR/Cas9 system for genome editing in mice, the pace of loss-of-function analysis has accelerated significantly. This has led to the identification of numerous genes that play crucial roles in male reproductive processes, including meiosis, chromatin condensation, flagellum formation in the testis, sperm maturation in the epididymis, and fertilization in the oviduct. Despite the advancements, the functions of many genes, particularly those enriched in male reproductive tissues, remain largely unknown. In our study, we focused on 15 genes and generated 13 gene-deficient mice [4933411K16Rik, Adam triple (Adam20, Adam25, and Adam39), BC048671, Cfap68, Gm4846, Gm4984, Gm13570, Nt5c1b, Ppp1r42, Saxo4, Sh3d21, Spz1, and Tektl1] to elucidate their roles in male fertility. Surprisingly, all 13 gene-deficient mice exhibited normal fertility in natural breeding experiments, indicating that these genes are not essential for male fertility. These findings have important implications as they may help prevent other research laboratories from duplicating efforts to generate knockout mice for genes that do not demonstrate an apparent phenotype related to male fertility. By shedding light on the dispensability of these genes, our study contributes to a more efficient allocation of research resources in the exploration of male reproductive biology

BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection

Shoko Kitada, Hisako Kayama, Daisuke Okuzaki, Ritsuko Koga, Masao Kobayashi, Yasunobu Arima, Atsushi Kumanogoh, Masaaki Murakami, Masahito Ikawa, Kiyoshi Takeda; BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection. J Exp Med 1 May 2017; 214 (5): 1313–1331. doi: https://doi.org/10.1084/jem.2016107

Suppression of HBV replication by the expression of nickase-and nuclease dead-Cas9

Kurihara, T., Fukuhara, T., Ono, C. et al. Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9. Sci Rep 7, 6122 (2017). https://doi.org/10.1038/s41598-017-05905-

Calaxin is required for cilia-driven determination of vertebrate laterality

Sasaki, K., Shiba, K., Nakamura, A. et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol 2, 226 (2019). https://doi.org/10.1038/s42003-019-0462-

トクシマ シミン ビョウイン ノ トリクミ

Since the innovation of the Diagnosis Procedure Combination（DPC）system at the TokushimaMunicipal Hospital in 2008, we have encountered shortening of average hospitalization and developedbetter medical standardization measures.Cancer patients tend to visit several hospitals because they expect special cancer treatment,and it becomes difficult to devote enough time for them in the outpatient clinic.At the hospital, medical care cooperation is provided through a team approach, and the work isshared among medical staff such as the pharmacist, nurse, and medical social worker. However, itis necessary to discuss the patients’ medical care issues with their respective family doctors toresolve these problems.We report the regional critical pathway at the Tokushima Municipal Hospital as a tool for familydoctors to cooperate in the care of cancer patients

精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved