• Growth differentiation factor 8 (GDF8), also known as myostatin (MSTN), is a secreted ligand of the TGF-beta superfamily that negatively regulates skeletal muscle growth, muscle cell proliferation, and differentiation.
• GDF8/myostatin signaling restrains satellite-cell activation and protein synthesis, making GDF8 a key therapeutic target for muscle wasting, sarcopenia, cachexia, obesity, and body composition research.
• B-hGDF8 mice are target-humanized mice in which exons 1-3 of the mouse Gdf8 gene encoding the full-length protein were replaced by human GDF8 exons 1-3.
• B-hGDF8 mice express human GDF8 mRNA in skeletal muscle and maintain circulating GDF8 protein detectable by ELISA, supporting translational evalsuation of human GDF8-targeted therapeutics.
• B-hGDF8 mice are suitable for preclinical pharmacology and efficacy studies of human GDF8/myostatin-targeted antibodies, inhibitors, and other biologics for muscle and metabolic disease research.

Key Advantages

• Humanized GDF8/myostatin target for translational drug evalsuation
• Human GDF8 mRNA expression confirmed in skeletal muscle
• Circulating GDF8 protein detectable in plasma by ELISA
• Supports anti-GDF8 antibody and myostatin inhibitor efficacy studies
• Applicable to muscle growth, obesity, and body composition research

Validation

• Molecular Validation: Human GDF8 mRNA was detectable in homozygous B-hGDF8 mice by RT-PCR, while mouse Gdf8 mRNA was detectable in wild-type C57BL/6 mice.
• Protein Validation: Plasma GDF8 protein was detected in homozygous B-hGDF8 mice by ELISA; GDF8 was also detectable in wild-type C57BL/6 mice because the ELISA kit cross-recognizes human and mouse GDF8.
• Efficacy Validation: In HFD-induced B-hGDF8 mice, anti-GDF8 monoclonal antibody treatment promoted lean tissue growth and helped prevent semaglutide-induced lean tissue loss, supporting in vivo evalsuation of GDF8-targeted therapeutics.

Application

• GDF8/myostatin-targeted drug development
• Anti-GDF8 antibody efficacy evalsuation
• Myostatin inhibitor pharmacology studies
• Muscle wasting, sarcopenia, cachexia, and muscle growth research
• Obesity, body composition, and metabolic disease studies

In B-hGDF8 mice, exons 1-3 of the mouse Gdf8 gene encoding the full-length GDF8 protein were replaced by human GDF8 exons 1-3. This gene humanization strategy enables expression of human GDF8/myostatin while preserving endogenous mouse gene regulation.
B-hGDF8 mice are generated on a C57BL/6N background (C57BL/6N-Gdf8tm1(GDF8)Bcgen/Bcgen, Cat# 112413). B-hGDF8 mice provide a translational in vivo model for evalsuating human GDF8-targeted antibodies, myostatin inhibitors, and other therapeutics designed to modulate muscle growth and metabolic phenotypes.

Strain-specific GDF8 protein expression was analyzed in homozygous B-hGDF8 mice by ELISA.
Plasma was collected from wild-type C57BL/6JNifdc mice (+/+), homozygous B-hGDF8 mice (H/H) (male, 6-week-old), and B-Gdf8 KO mice (-/-), and analyzed by ELISA. Human and mouse GDF8 proteins were both detectable in wild-type C57BL/6JNifdc and B-hGDF8 mice, but not in B-Gdf8 KO mice. The ELISA kit cross-recognizes human and mouse GDF8, supporting measurable circulating GDF8 protein expression in B-hGDF8 mice.

Strain-specific analysis of GDF8 mRNA expression was performed in wild-type C57BL/6 mice and B-hGDF8 mice by RT-PCR.
Skeletal muscle RNA was isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hGDF8 mice (H/H). cDNA libraries were synthesized by reverse transcription followed by PCR using mouse- or human-specific GDF8 primers. Mouse Gdf8 mRNA was detectable only in wild-type C57BL/6 mice. Human GDF8 mRNA was detectable only in homozygous B-hGDF8 mice but not in wild-type mice.

In vivo efficacy of GDF8-targeted antibody treatment was evalsuated in high-fat diet (HFD)-induced B-hGDF8 mice.
B-hGDF8 mice were fed a high-fat diet for 14 weeks to induce obesity, and body weight and body composition were monitored during treatment. After treatment, body weight, lean tissue change, and fat tissue change were analyzed by body composition analyzer.
The anti-GDF8 monoclonal antibody promoted lean tissue growth and, in combination with semaglutide, helped prevent semaglutide-induced lean tissue loss in B-hGDF8 mice. Values are expressed as mean ± SEM.
Note: Data allowed to be shared by the clients.

Q1: What are B-hGDF8 mice?

B-hGDF8 mice are gene-humanized mice in which exons 1-3 of the mouse Gdf8 gene were replaced by human GDF8 exons 1-3, enabling human GDF8/myostatin-targeted drug evalsuation in vivo.

Q2: Why is GDF8 an important therapeutic target?

GDF8, also known as myostatin, is a negative regulator of skeletal muscle growth. Targeting GDF8 is a promising strategy for muscle wasting, sarcopenia, cachexia, obesity, and body composition research.

Q3: How was B-hGDF8 mice validated?

Human GDF8 mRNA was confirmed in skeletal muscle by RT-PCR, and circulating GDF8 protein was detected in plasma by ELISA in homozygous B-hGDF8 mice.

Q4: Can B-hGDF8 mice be used for antibody efficacy studies?

Yes. B-hGDF8 mice support in vivo evalsuation of GDF8-targeted antibodies and myostatin inhibitors, including HFD-induced studies assessing body weight, lean tissue, and fat tissue changes.

Q5: What are the main applications of B-hGDF8 mice?

Applications include GDF8/myostatin-targeted drug development, anti-GDF8 antibody efficacy evalsuation, muscle growth research, obesity studies, and metabolic disease research.