Corneal Changes and Strategies to Improve Survival of Hypomorphic Collagen VII-Deficient Mice for the Study of Ocular Dystrophic Epidermolysis Bullosa.

Document Type

Article

Publication Date

2-1-2022

Publication Title

Comparative medicine

Keywords

JGM, Animals, Collagen, Corneal Opacity, Epidermolysis Bullosa Dystrophica, Eye, Female, Fibrosis, Male, Mice

JAX Source

Comp Med 2022 Feb 1; 72(1):14-21

Volume

72

Issue

1

First Page

14

Last Page

21

ISSN

1532-0820

PMID

35131003

DOI

https://doi.org/10.30802/aalas-cm-21-000063

Abstract

Ophthalmic study of collagen CVII hypomorphic mice is uniquely challenging due to the strain's published survival rate to weaning of 24%. Because chronic ocular fibrosis requires time to develop, optimizing the survival rate is of critical importance. In this study, standard husbandry practices were enhanced by the addition of sterilized diet and drug delivery gels, acidified water, irradiated food pellets, cellulose fiber bedding, minimal handling, removal of siblings within 2-3 wk from birth, and a preferred housing location. Survival rates per breeding cycle, sex, weight, and cause of early euthanasia were recorded and analyzed over 43 mo. Overall, 49% of mice survived to weaning and 76% of weaned mice survived to 20 wk of age. Corneal opacities were seen in 65% of mice by 20 wk, but only 10% of eyes showed the sustained opacification that was indicative of fibrosis. Corneal opacities occurred at the same rate as in humans with epidermolysis bullosa. 66% of the mice showed weight loss at 11 wk. Males required early euthanasia 4 times more often than did females. Euthanasia was required for urinary obstruction due to penile prolapse in 88% of males. With our enhanced care protocol, hypomorphic mice in our colony survived at twice the published rate. With this revised husbandry standard, experiments planned with termination endpoints of 14 wk for males and 17 wk for females are more likely to reach completion.

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