Inactivation of Stac3 causes skeletal muscle defects and perinatal death in mice

The Src homology 3 domain (SH3) and cysteine rich domain (C1) 3 (Stac3) gene is a novel gene copiously expressed in skeletal muscle. The objective of this research was to determine the role of Stac3 in development, specifically in skeletal muscle. We achieved this objective by evaluating the phenotypic effects of Stac3 gene inactivation on development in mice. At birth homozygous Stac3 null (Stac3-/-) mice died perinatally and remained in fetal position with limp limbs, but possessed otherwise normal organs based on gross and histological evaluations. The primary phenotypes displayed at term in Stac3-/- mice were reduced late gestational body weights, increased prevalence of myotubes with centrally located nuclei and severe deformities throughout all skeletal muscles. At embryonic day 18.5 (E18.5) Stac3-/- mice displayed a 12.7% reduction (P < 0.001) in weight compared to wild type (Stac3+/+) or heterozygous (Stac3+/-) littermates while at E15.5 body weights and morphology were similar. At birth (P0) and at E17.5, Stac3-/- mice had 59% and 24% (P < 0.001) more myotubes with centrally located nuclei, respectively, than Stac3+/- or Stac3+/+ littermates. Stac3-/- mice also displayed increased myotube and myofiber cross sectional area at P0 (P < 0.001) and E17.5 (P < 0.05) with disorganized fiber bundling. Overall, these data show Stac3 is necessary for development of viable offspring and suggest Stac3 plays a critical role in fetal development where its primary phenotype is exhibited in skeletal muscle.

Name thesis:degree_name

Master of Science in Life Sciences

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Animal and Poultry Sciences

Department dc:contributor.department

Animal and Poultry Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2012

Author dc:creator

• Reinholt, Brad Michael

Chairs dc:contributor.committeechair

• Jiang, Honglin
• Gerrard, David E.

Committee member dc:contributor.committeemember

• Grant, Alan L.

• SH3 domain
• C1 domain
• myogenesis
• SH3 and cysteine rich domain 3 (Stac3)

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en_US

Dc Identifier Other

etd-02102012-112645

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/76784