Related Experiment Video
Updated: Feb 6, 2026
Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease
Published on: July 18, 2019
Analysis of Keratoconus-Related Phenotypes in Two Pcsk1 Mouse Models
Carol Beatty1, Jingwen Cai2,3, Hongfang Yu2
1Medical College of Georgia, Augusta University, Augusta, GA, USA.
Purpose:
Previously, a variant within the Pcsk1 gene was found to segregate with the keratoconus (KC) phenotype in whole genome sequencing of a four-generation family. We aimed to evaluate a potential relation between the Pcsk1 gene and corneal phenotype in mouse models.
Methods:
Two strains of Pcsk1 mice, one with a knockout (KO) and one with an N222D point mutation, were bred. Central corneal thickness (CCT) was determined using spectral domain optical coherence tomography (SD-OCT) in PC1/3+/+ (n = 12), PC1/3+/K^ (n = 14), PC1/3K^/K^ (n = 5), PC1+/+ (n = 8), PC1+/ N222D (n = 15), and PC1 N222D / N222D (n = 7) mice at 3 and 6 months of age. Pachymetry maps were generated using the Mouse Corneal Analysis Program (MCAP) to process OCT images. Hematoxylin and eosin (H&E) staining using corneal sections from these animals were used to examine morphological changes.
Results:
No significant differences in corneal CCT, pachymetry, or morphology were observed among any of the mutant mice compared with their control littermates.
Conclusions:
In this setting, neither the N222D point mutation nor the Pcsk1 KO affected the corneal phenotype in two mouse models. The Pcsk1 gene could contribute to keratoconus when paired with additional genetic and environmental factors, not included in this study.
Translational Relevance:
Genetic factors are known to contribute to the pathogenesis of keratoconus. Although a variant in the Pcsk1 gene has been shown to segregate with keratoconus in a family, there is yet no evidence of Pcsk1 gene mutation correlating with pathogenic corneal phenotype in mouse models.
Related Concept Videos
02:27Background and Environment Affect Phenotype
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
01:23Mechanistic Models: Compartment Models in Individual and Population Analysis
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
01:35Pedigree Analysis
01:14Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...