1 Laboratory Animal Resource Center, 204180 Korea Research Institute of Bioscience and Biotechnology , Chungbuk 28116, Korea.
2 Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Chungbuk 28644, Korea.
Exp Biol Med (Maywood). 2018 Mar;243(5):408-417. doi: 10.1177/1535370218758249. Epub 2018 Feb 6.
FRY like transcription coactivator ( Fryl) gene located on chromosome 5 is a paralog of FRY microtubule binding protein ( Fry) in vertebrates. It encodes a protein with unknown functions. Fryl gene is conserved in various species ranging from eukaryotes to human. Although there are several reports on functions of Fry gene, functions of Fryl gene remain unclear. A mouse line containing null mutation in Fryl gene by gene trapping was produced in this study for the first time. The survival and growth of Fryl mice were observed. Fryl gene expression levels in mouse tissues were determined and histopathologic analyses were conducted. Most Fryl mice died soon after birth. Rare Fryl survivors showed growth retardation with significantly lower body weight compared to their littermate controls. Although they could breed, more than half of Fryl survivors died of hydronephrosis before age 1. No abnormal histopathologic lesion was apparent in full-term embryo or adult tissues except the kidney. Abnormal lining cell layer detachments from walls of collecting and convoluted tubules in kidneys were apparent in Fryl neonates and full-term embryos. Fryl gene was expressed in renal tubular tissues including the glomeruli and convoluted and collecting tubules. This indicates that defects in tubular systems are associated with Fryl functions and death of Fryl neonates. Fryl protein is required for normal development and functional maintenance of kidney in mice. This is the first report of in vivo Fryl gene functions. Impact statement FRY like transcription coactivator ( Fryl) gene is conserved in various species ranging from eukaryotes to human. It expresses a protein with unknown function. We generated a Fryl gene mutant mouse line and found that most homozygous mice died soon after their birth. Rare Fryl survivors showed growth retardation with significantly lower body weight compared to their littermate controls. Although they could breed, more than half of Fryl survivors died of hydronephrosis before age 1. Full-term mutant embryos showed abnormal collecting and convoluted tubules in kidneys where Fryl gene was expressed. Collectively, these results indicate that Fryl protein is required for normal development and functional maintenance of kidney in mice. To the best of our knowledge, this is the first report on in vivo Fryl gene functions.
FRY 样转录共激活因子（Fryl）基因位于 5 号染色体上，是脊椎动物 FRY 微管结合蛋白（Fry）的同源基因。它编码一种具有未知功能的蛋白质。Fryl 基因在从真核生物到人类的各种物种中都有保守。尽管有几个关于 Fry 基因功能的报告，但 Fryl 基因的功能仍不清楚。本研究首次通过基因捕获产生了 Fryl 基因缺失突变的小鼠品系。观察了 Fryl 小鼠的生存和生长情况。测定了小鼠组织中 Fryl 基因的表达水平，并进行了组织病理学分析。大多数 Fryl 小鼠在出生后不久就死亡。极少数 Fryl 存活者生长迟缓，体重明显低于同窝对照。尽管它们可以繁殖，但超过一半的 Fryl 存活者在 1 岁前死于肾积水。除了肾脏，足月胚胎或成年组织中没有明显的异常组织病理学病变。在 Fryl 新生儿和足月胚胎中，肾脏的集合管和卷曲小管的衬里细胞层从管壁上明显分离。Fryl 基因在包括肾小球和卷曲小管和集合小管在内的肾小管组织中表达。这表明管状系统的缺陷与 Fryl 功能有关，也是 Fryl 新生儿死亡的原因。Fryl 蛋白是小鼠肾脏正常发育和功能维持所必需的。这是 Fryl 基因体内功能的首次报道。影响说明 FRY 样转录共激活因子（Fryl）基因在从真核生物到人类的各种物种中都有保守。它表达一种具有未知功能的蛋白质。我们生成了 Fryl 基因突变小鼠品系，发现大多数纯合子小鼠在出生后不久就死亡。极少数 Fryl 存活者生长迟缓，体重明显低于同窝对照。尽管它们可以繁殖，但超过一半的 Fryl 存活者在 1 岁前死于肾积水。足月突变胚胎的肾脏显示出异常的集合管和卷曲小管，Fryl 基因在这些部位表达。总的来说，这些结果表明 Fryl 蛋白是小鼠肾脏正常发育和功能维持所必需的。据我们所知，这是关于 Fryl 基因体内功能的首次报道。
