Open AccessConditional Deletion of Cytoplasmic Dynein Heavy Chain in Postnatal Photoreceptors
Author(s) -
Tiffanie Dahl,
Michelle Reed,
Cecilia D. Gerstner,
Wolfgang Baehr
Publication year - 2021
Publication title -
investigative ophthalmology and visual science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.935
H-Index - 218
eISSN - 1552-5783
pISSN - 0146-0404
DOI - 10.1167/iovs.62.14.23
Subject(s) - dynein , microbiology and biotechnology , cytoplasm , chain (unit) , heavy chain , biology , biophysics , chemistry , physics , genetics , microtubule , gene , astronomy
Purpose Cytoplasmic dynein-1 (henceforth dynein) moves cargo in conjunction with dynactin toward the minus end of microtubules. The dynein heavy chain, DYNC1H1, comprises the backbone of dynein, a retrograde motor. Deletion of Dync1h1 abrogates dynein function. The purpose of this communication is to demonstrate effects of photoreceptor dynein inactivation during late postnatal development and in adult retina. Methods We mated Dync1h1 F/F mice with iCre75 and Prom1-CreER T2 mice to generate conditional rod and tamoxifen-induced knockout in rods and cones, respectively. We documented retina degeneration with confocal microscopy at postnatal day (P) 10 to P30 for the iCre75 line and 1 to 4 weeks post tamoxifen induction (wPTI) for the Prom1-CreER T2 line. We performed scotopic and photopic electroretinography (ERG) at P16 to P30 in the iCre75 line and at 1-week increments in the Prom1-CreER T2 line. Results were evaluated statistically using Student's t -test, two-factor ANOVA, and Welch's ANOVA. Results Cre-induced homologous recombination of Dync1h1 F/F mice truncated DYNC1H1 after exon 23. rod Dync1h1 −/− photoreceptors degenerated after P14, reducing outer nuclear layer (ONL) thickness and combined inner segment/outer segment (IS/OS) length significantly by P18. Scotopic ERG a-wave amplitudes decreased by P16 and were extinguished at P30. Cones were stable under rod-knockout conditions until P21 but inactive at P30. In tam Dync1h1 −/− photoreceptors, the IS/OS began shortening by 3wPTI and were nearly eliminated by 4wPTI. The ONL shrank significantly over this interval, indicating rapid photoreceptor degeneration following the loss of dynein. Conclusions Our results demonstrate dynein is essential for the secretory pathway, formation of outer segments, and photoreceptor maintenance.