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Updated: May 20, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Generation and characterization of Tmeff2 mutant mice
Tian Rui Chen1, Ping Wang, Liberty K Carroll
1Department of Cell Biology, Duke University Medical Center, Box 3709, Durham, NC 27710, USA.
Abstract:
TMEFF2 is a single-transmembrane protein containing one EGF-like and two follistatin-like domains. Some studies implicated TMEFF2 as a tumor suppressor for prostate and other cancers, whereas others reported TMEFF2 functioning as a growth factor for neurons and other cells. To gain insights into the apparently conflicting roles of TMEFF2, we generated a null allele of Tmeff2 gene by replacing its first coding exon with human placental alkaline phosphatase cDNA (Tmeff2(PLAP)). Tmeff2(PLAP/PLAP) homozygous mutant mice are born normal, but show growth retardation and die around weaning age. Tmeff2 is widely expressed in the nervous system, and the Tmeff2(PLAP) knock-in allele enables the visualization of neuronal innervations of skin and internal organs with a simple alkaline phosphatase staining. Tmeff2 is also highly expressed in prostate gland and white adipose tissues (WAT). However, with the exception of reduced WAT mass, extensive anatomical and molecular analyses failed to detect any structural or molecular abnormalities in the brain, the spinal cord, the enteric nervous system, or the prostate in the Tmeff2 mutants. No tumors were found in Tmeff2-mutant mice. The Tmeff2(PLAP/PLAP) knock-in mouse is an useful tool for studying the in vivo biological functions of TMEFF2.
Insights
The TMEFF2 gene
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.
