Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Department of Ophthalmology and Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2018 Jul 3;13(7):e0199824. doi: 10.1371/journal.pone.0199824. eCollection 2018.
Surfactant proteins are important collectin immune molecules with a wide distribution throughout the body, including the ocular system. Mice with gene deletions for the surfactant protein genes Sftpa1 and Sftpd were observed to have visual impairment and thinning of the outer nuclear layers of the retina. We hypothesized that gene deletion of Sftpa1 and Sftpd (Sftpa1tm1Kor/J and Sftpd-/-) results in early retinal degeneration in these mice. Sftpa1tm1Kor/J and Sftpd-/- retinas were evaluated by histopathology and optical coherence tomography (OCT). Retinas from Sftpa1tm1Kor/J and Sftpd -/- mice showed early retinal degeneration with loss of the outer nuclear layer. After screening of mice for known retinal degeneration mutations, the mice were found to carry a previously unrecognized Pde6brd1 genotype which resulted from earlier breeding of the strain with Black Swiss mice during their generation. The mutation was outbred and the genotype of Sftpa1tm1Kor/J and Sftpd-/- was confirmed. Outbreeding of the Pde6brd1 mutation resulted in restoration of normal retinal architecture confirmed by in vivo and in vitro examination. We can therefore conclude that loss of Sftpa1 and Sftpd do not result in retinal degeneration. We have now generated retinal Sftpa1 and Sftpd targeted mice that exhibit normal retinal histology.
表面活性蛋白是重要的集落刺激因子免疫分子，在全身广泛分布，包括眼部系统。观察到表面活性蛋白基因 Sftpa1 和 Sftpd 基因缺失的小鼠有视力障碍和视网膜外核层变薄。我们假设 Sftpa1 和 Sftpd 基因缺失（Sftpa1tm1Kor/J 和 Sftpd-/-）会导致这些小鼠的早期视网膜变性。通过组织病理学和光学相干断层扫描（OCT）评估 Sftpa1tm1Kor/J 和 Sftpd-/-的视网膜。Sftpa1tm1Kor/J 和 Sftpd -/- 小鼠的视网膜显示出早期的视网膜变性，外核层丢失。在对已知的视网膜变性突变进行筛选后，发现这些小鼠携带一种以前未被识别的 Pde6brd1 基因型，这是由于该品系在其产生过程中与瑞士黑牛进行了早期杂交。突变被杂交，Sftpa1tm1Kor/J 和 Sftpd-/-的基因型得到了确认。Pde6brd1 突变的杂交导致正常视网膜结构的恢复，通过体内和体外检查得到证实。因此，我们可以得出结论，Sftpa1 和 Sftpd 的缺失不会导致视网膜变性。我们现在已经生成了具有正常视网膜组织学的视网膜 Sftpa1 和 Sftpd 靶向小鼠。
