RGD Reference Report - Spontaneous testicular atrophy occurs despite normal spermatogonial proliferation in a Tp53 knockout rat. - Rat Genome Database

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Spontaneous testicular atrophy occurs despite normal spermatogonial proliferation in a Tp53 knockout rat.

Authors: Dai, M S  Hall, S J  Vantangoli Policelli, M M  Boekelheide, K  Spade, D J 
Citation: Dai MS, etal., Andrology. 2017 Nov;5(6):1141-1152. doi: 10.1111/andr.12409. Epub 2017 Aug 22.
RGD ID: 14995504
Pubmed: PMID:28834365   (View Abstract at PubMed)
PMCID: PMC5673550   (View Article at PubMed Central)
DOI: DOI:10.1111/andr.12409   (Journal Full-text)

The tumor suppressor protein p53 (TP53) has many functions in cell cycle regulation, apoptosis, and DNA damage repair and is also involved in spermatogenesis in the mouse. To evaluate the role of p53 in spermatogenesis in the rat, we characterized testis biology in adult males of a novel p53 knockout rat (SD-Tp53tm1sage ). p53 knockout rats exhibited variable levels of testicular atrophy, including significantly decreased testis weights, atrophic seminiferous tubules, decreased seminiferous tubule diameter, and elevated spermatocyte TUNEL labeling rates, indicating a dysfunction in spermatogenesis. Phosphorylated histone H2AX protein levels and distribution were similar in the non-atrophic seminiferous tubules of both genotypes, showing evidence of pre-synaptic DNA double-strand breaks in leptotene and zygotene spermatocytes, preceding cell death in p53 knockout rat testes. Quantification of the spermatogonial stem cell (SSC) proliferation rate with bromodeoxyuridine (BrdU) labeling, in addition to staining with the undifferentiated type A spermatogonial marker GDNF family receptor alpha-1 (GFRA1), indicated that the undifferentiated spermatogonial population was normal in p53 knockout rats. Following exposure to 0.5 or 5 Gy X-ray, p53 knockout rats exhibited no germ cell apoptotic response beyond their unirradiated phenotype, while germ cell death in wild-type rat testes was elevated to a level similar to the unexposed p53 knockout rats. This study indicates that seminiferous tubule atrophy occurs following spontaneous, elevated levels of spermatocyte death in the p53 knockout rat. This phenomenon is variable across individual rats. These results indicate a critical role for p53 in rat germ cell survival and spermatogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IMP 14995504 RGD 
response to X-ray  IMP 14995504 RGD 
spermatogenesis  IMP 14995504 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Tp53  (tumor protein p53)
Tp53em1Sage  (tumor protein p53; ZFN induced mutant 1, Sage)

Genes (Mus musculus)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
TP53  (tumor protein p53)

SD-Tp53em1Sage  (NA)

Additional Information