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

Area of Science:

• Immunology
• Ophthalmology
• Genetics

Background:

• Surfactant proteins (collectins) are immune molecules found throughout the body, including the eyes.
• Previous observations in mice lacking Sftpa1 and Sftpd genes suggested potential visual impairment and retinal thinning.

Purpose of the Study:

• To investigate the hypothesis that gene deletion of surfactant protein A1 (Sftpa1) and D (Sftpd) leads to early retinal degeneration.
• To clarify the role of Sftpa1 and Sftpd in maintaining retinal structure and function.

Main Methods:

• Histopathological examination of retinas from Sftpa1tm1Kor/J and Sftpd-/- mice.
• Optical coherence tomography (OCT) for in vivo retinal imaging.
• Screening for known retinal degeneration mutations and genetic outbreeding.

Main Results:

• Initial examination of Sftpa1tm1Kor/J and Sftpd-/- retinas indicated early degeneration with outer nuclear layer loss.
• A previously unrecognized Pde6brd1 genotype, arising from strain breeding, was identified as the cause of the observed retinal phenotype.
• Outbreeding the Pde6brd1 mutation restored normal retinal architecture in the genetically modified mice.

Conclusions:

• Loss of Sftpa1 and Sftpd alone does not cause retinal degeneration.
• The study successfully generated Sftpa1 and Sftpd targeted mice with normal retinal histology after correcting for confounding genetic factors.