Abdul-Majeed Shakila, Mell Blair, Nauli Surya M, Joe Bina
Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, United States of America.
Department of Pharmacology, University of Toledo College of Pharmacy, Toledo, Ohio, United States of America.
PLoS One. 2014 Jul 1;9(7):e100967. doi: 10.1371/journal.pone.0100967. eCollection 2014.
A Disintegrin And Metalloproteinase with ThromboSpondin motifs16 (ADAMTS-16) is a member of a family of metalloproteinases. Using a novel zinc-finger nuclease based gene-edited rat model harboring a targeted mutation of the Adamts16 locus, we previously reported this gene to be linked to blood pressure regulation. Here we document our observation with this model that Adamts16 is essential for normal development of the testis. Absence of Adamts16 in the homozygous Adamts16mutant males resulted in cryptorchidism and male sterility. Heterozygous Adamts16mutant males were normal, indicating that this is a recessive trait. Testes of homozygous Adamts16mutant males were significantly smaller with significant histological changes associated with the lack of sperm production. Temporal histological assessments of the testis demonstrated that the seminiferous tubules did not support active spermatogenesis, but progressively lost germ cells, accumulated vacuoles and did not have any sperm. These observations, taken together with our previous report of renal abnormalities observed with the same Adamts16mutant rats, suggest an important mechanistic link between Adamts16 and the functioning of the male genitourinary system.
含血小板反应蛋白基序的解聚素和金属蛋白酶16（ADAMTS - 16）是金属蛋白酶家族的成员。利用一种新型的基于锌指核酸酶的基因编辑大鼠模型，该模型携带Adamts16基因座的靶向突变，我们之前报道该基因与血压调节有关。在此，我们用这个模型记录了我们的观察结果，即Adamts16对睾丸的正常发育至关重要。纯合Adamts16突变雄性大鼠中Adamts16的缺失导致隐睾症和雄性不育。杂合Adamts16突变雄性大鼠是正常的，表明这是一种隐性性状。纯合Adamts16突变雄性大鼠的睾丸明显较小，伴有与精子生成缺乏相关的显著组织学变化。对睾丸进行的时间性组织学评估表明，生精小管不支持活跃的精子发生，而是逐渐失去生殖细胞，积累空泡，且没有任何精子。这些观察结果，连同我们之前对同一Adamts16突变大鼠所观察到的肾脏异常报告，表明Adamts16与男性生殖泌尿系统功能之间存在重要的机制联系。
