Dataset Information

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.

SUBMITTER: Lubkemann A

PROVIDER: S-EPMC8276586 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The G6PC3 gene encodes the ubiquitously expressed glucose-6-phosphatase enzyme (G-6-Pase ? or G-6-Pase 3 or G6PC3). Bi-allelic G6PC3 mutations cause a multi-system autosomal recessive disorder of G6PC3 deficiency (also called severe congenital neutropenia type 4, MIM 612541). To date, at least 57 patients with G6PC3 deficiency have been described in the literature.G6PC3 deficiency is characterized by severe congenital neutropenia, recurrent bacterial infections, intermittent thrombocytopenia in many patients, a prominent superficial venous pattern and a high incidence of congenital cardiac defects and uro-genital anomalies. The phenotypic spectrum of the condition is wide and includes rare manifestations such as maturation arrest of the myeloid lineage, a normocellular bone marrow, myelokathexis, lymphopaenia, thymic hypoplasia, inflammatory bowel disease, primary pulmonary hypertension, endocrine abnormalities, growth retardation, minor facial dysmorphism, skeletal and integument anomalies amongst others. Dursun syndrome is part of this extended spectrum. G6PC3 deficiency can also result in isolated non-syndromic severe neutropenia. G6PC3 mutations in result in reduced enzyme activity, endoplasmic reticulum stress response, increased rates of apoptosis of affected cells and dysfunction of neutrophil activity.In this review we demonstrate that loss of function in missense G6PC3 mutations likely results from decreased enzyme stability. The condition can be diagnosed by sequencing the G6PC3 gene. A number of G6PC3 founder mutations are known in various populations and a possible genotype-phenotype relationship also exists. G6PC3 deficiency should be considered as part of the differential diagnoses in any patient with unexplained congenital neutropenia.Treatment with G-CSF leads to improvement in neutrophil numbers, prevents infections and improves quality of life. Mildly affected patients can be managed with prophylactic antibiotics. Untreated G6PC3 deficiency can be fatal. Echocardiogram, renal and pelvic ultrasound scans should be performed in all cases of suspected or confirmed G6PC3 deficiency. Routine assessment should include biochemical profile, growth profile and monitoring for development of varicose veins or venous ulcers.