Gene expression profiling of myostatin null mice

Increasing muscle growth is beneficial to the meat animal industry and for biomedical research. Altering myostatin function and administration of β-adrenergic agonists, such as clenbuterol, enhances muscle growth. However, it is unclear whether the mechanisms of these effects converge in a single pathway. Previous work demonstrated that myostatin null mice (MKO) did respond to clenbuterol with increased body and muscle weights suggesting disparate mechanisms for each effect. We examined gene expression profiles of these mice to identify downstream targets of myostatin null- and clenbuterol-induced skeletal muscle hypertrophy. Microarray analysis was not successful at identifying gene expression differences between clenbuterol-treated and control mice. Differences in gene expression between the MKO mice and wild type (WT) mice were observed including changes in genes related to amino acid and derivative metabolism - specifically creatine biosynthesis and metabolism, development, muscle contraction, transport, and Wnt receptor signaling. Real Time PCR (RT-PCR) was employed to validate genes associated with each of these processes in the tibialis anterior, gastrocnemius, and soleus muscles. Additionally, creatine content and creatine kinase (CK) activity was directly measured in the tibialis anterior and gastrocnemius muscles. Expression of nearly all genes investigated was consistent with microarray analysis, as was expression of myosin heavy chain isoforms. Furthermore, creatine and creatine kinase activity were increased in myostatin null mice compared with wild type mice. Therefore this experiment confirms the role of myostatin as a negative regulator of muscle mass and also demonstrates some of the downstream effects of skeletal muscle hypertrophy associated with the myostatin null mutation.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2010

Author dc:creator

• Gabriel, Savannah

Contributors dc:contributor

• Killefer, John

• myostatin
• mice
• gene expression
• skeletal muscle hypertrophy
• clenbuterol

Statement dc:rights

• Copyright 2009 Savannah Gabriel

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/14628

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/14628