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| Status |
Public on Mar 28, 2013 |
| Title |
Disruption of Ttll5/Stamp gene (Tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2 associated modulatory protein gene) in male mice causes sperm malformation and infertility |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Tubulin tyrosine ligase-like family member 5 (TTLL5/STAMP) has multiple activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid receptor-regulated gene induction and repression, and displays steroid-independent growth activity with several cell types. To examine TTLL5/STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene. This mutation causes both reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein. Homozygous targeted mutant (Stamptm/tm) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility. Abnormal axonemal structures with loss of tubulin doublets occur in most Stamptm/tm sperm tails in conjunction with substantial reduction in tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA. The axonemes in other structures appear unaffected. There is no obvious change in the organs for sperm development of wt vs. Stamptm/tm males despite the levels of wt STAMP mRNA in testes being 20-fold higher than in any other organ examined. This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function. Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated pathway for tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility.
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| Overall design |
Testes RNA samples for EXON arrays from WT and KO with three biological replications
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| Contributor(s) |
Lee G, He Y, Dougherty EJ, Jimenez-Movilla M, Avella M, Grullon S, Sharlin DS, Guo C, Blackford JA, Awasthi S, Zhang Z, Armstrong SP, London EC, Chen W, Dean J, Simons SS |
| Citation(s) |
23558686 |
| Submission date |
Mar 27, 2013 |
| Last update date |
Mar 03, 2017 |
| Contact name |
WeiPing Chen |
| E-mail(s) |
weipingChen@niddk.nih.gov
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| Phone |
301-496-0175
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| Organization name |
NIDDK/NIH
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| Department |
GCL
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| Lab |
Genomics Core Lab
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| Street address |
Bldg 8, Room 1A11, NIDDK/NIH
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL6193 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [probe set (exon) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA194559 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45546_RAW.tar |
244.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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