Cardiac Morphology and Collagen Deposition in A Glucose-6-Phosphatase Catalytic Subunit 3 (G6PC3) Knockout Mouse model

Abstract

Background: Glucose-6-phosphatase-- β (3), one of multiple isoforms of glucose-6-phosphatase, catalyzes the final step in gluconeogenesis. It is known that mutated G6P3 is associated with severe neutropenia in addition to congenital heart defects, but little is known about the histological changes in cardiac tissue as a result of mutated or deleted G6PC34. Objectives: We sought to further characterize the histological alterations caused by deleted G6PC3 and determine the role of collagen deposition, myocyte proliferation and apoptosis in these changes. Methods: Cardiac tissue from G6PC3 knockout mice and WT mice were harvested, imbedded and stained for markers of collagen (Trichrome), proliferation (KI-67), apoptosis (caspase 3) and hematopoietic stem cells (CD34). Slides were digitally uploaded, and Leica stain quantification was calculated. Results: We demonstrated that in G6PC3 knock out adult mice have significant differences in heart morphology including decreased left ventricular collagen, decreased cellular proliferation and increased apoptosis histologically. Conclusions: As compared to wild type, the hearts of G6PC3 knockout mice demonstrated significantly decreased collagen globally, a crucial component for adequate strength and contractility of myocardial tissue. More investigation should be done to further explore the functional effects of such alterations via echocardiograms.