Generation and characterization of Tmeff2 mutant mice

Area of Science:

• Molecular Biology
• Genetics
• Neuroscience

Background:

• The TMEFF2 protein has demonstrated contradictory roles in cancer suppression and cell growth.
• Understanding the in vivo functions of TMEFF2 is crucial for resolving these conflicting observations.

Purpose of the Study:

• To investigate the biological functions of the TMEFF2 gene in vivo.
• To generate and characterize a TMEFF2-deficient mouse model.

Main Methods:

• Generation of a Tmeff2 null allele using a knock-in strategy with human placental alkaline phosphatase (PLAP) reporter.
• Phenotypic analysis of Tmeff2(PLAP/PLAP) homozygous mutant mice, including anatomical and molecular assessments.
• Utilizing alkaline phosphatase staining for visualizing neuronal innervations.

Main Results:

• Tmeff2(PLAP/PLAP) mice exhibit growth retardation and mortality around weaning age.
• TMEFF2 is widely expressed in the nervous system, prostate, and white adipose tissue (WAT).
• Mutant mice showed reduced WAT mass but no significant structural or molecular abnormalities in the brain, spinal cord, enteric nervous system, or prostate; no tumors were observed.

Conclusions:

• The TMEFF2 gene plays a role in normal growth and development, with loss-of-function leading to growth retardation.
• The TMEFF2(PLAP) knock-in mouse model is a valuable tool for studying TMEFF2's in vivo functions and visualizing neural networks.
• The study did not support a tumor suppressor role for TMEFF2 in the prostate or other investigated tissues in this model.