|
General Comment |
NCBI Summary:
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]
|
|
Mutations |
1 mutations
Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Tissue-specific knockout of A-kinase anchoring protein 13 (AKAP13) – a potential murine model for polycystic ovarian syndrome
K. Devine, P.H. Driggers, T.J. Chu, A.H. DeCherney, J.H. SegarsBecause the null mutant of AKAP13 was embryonic lethal, we designed a Cre/LoxP conditional knockout system using Cre driven by Amhr2 and a floxed AKAP13 gene (CKO=AKAP13Flox/Flox/Cre+), to eliminate AKAP13 in granulosa cells. Mice were characterized using real-time RT-PCR, histomorphometry, and immunohistochemistry.
Results
At 6 weeks of age, the expected excised (mutant) AKAP13 allele was present in genomic DNA extracted from ovaries in CKO mice, but not in control littermates (such as AKAP13WT/WT/Cre+). Histologic evaluation of CKO ovaries demonstrated minimal intervening stroma, multiple follicles, and no clear evidence of ovulation. Mean section area was 37% smaller in CKO than in control ovaries (p<0.003). Real-time RT-PCR demonstrated 75% greater akap13 mRNA expression in whole ovary of control versus CKO (p<0.001, normalized with18S rRNA). Aromatase expression was also significantly decreased in CKO ovary (p<0.002).
Conclusion
Ovary-specific knockout of AKAP13 resulted in an in vivo phenotype that lacked evidence of ovulation and had decreased aromatase expression. This model has the potential to yield significant insight into various conditions marked by impaired folliculogenesis, such as polycystic ovary syndrome.
|