Retinal degeneration mutation in Sftpa1tm1Kor/J and Sftpd -/- targeted mice

Abstract

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.

In Vivo Imaging of Retinal and Choroidal Morphology and Vascular Plexuses of Vertebrates Using Swept-Source Optical Coherence Tomography

“…5 E), demonstrating good correlation between the retinal layers observed in vivo and in histology cross sections. 37 …”

“…( E ) Representative histological section of a C57BL/6J mouse retina. 37 ( Scale bars : Vertical = 300 µm; Horizontal = 50 µm).…”

Evaluation of Genomic and Proteomic Expression of Surfactant Protein D in the Mouse Retina

“…The generation and background of these mice have been reported previously in detail (15). PCR was used to determine the genotype of all pups prior to analysis (16). After confirmation of genotype, wild-type mice were euthanized, and their retinas were collected at postnatal day 0 (P0), P2, P5, P7, and P14, and in adulthood (ages varied from P48 to 6 months of age).…”

“…The primers for the detection of the knockout gene (KO) were developed based on the mouse created by Korfhagen et al by the integration of a vector neo nucleotide sequence. The neo sequence deletes the initiating methionine and translation initiation sequence ATG from the second exon (15, 16). For the rd1 mutation on the Pde6b gene, primers were used according to the methods of Blazek et al (17).…”