RGD Reference Report - Transgenic rescue of SF-1-null mice. - Rat Genome Database

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Transgenic rescue of SF-1-null mice.

Authors: Karpova, Tatiana  Maran, R R M  Presley, Jeremy  Scherrer, Serge P  Tejada, Lovella  Heckert, Leslie L 
Citation: Karpova T, etal., Ann N Y Acad Sci. 2005 Dec;1061:55-64.
RGD ID: 12904919
Pubmed: PMID:16467257   (View Abstract at PubMed)
PMCID: PMC1544363   (View Article at PubMed Central)
DOI: DOI:10.1196/annals.1336.007   (Journal Full-text)

Steroidogenic factor 1 (SF-1, Nr5a1, and Ad4bp) is an orphan nuclear receptor required for adrenal and gonad development and endocrine regulation. To extend our understanding of SF-1 function and the mechanisms controlling its expression, a transgenic rescue strategy was employed to locate important transcriptional control regions and to reveal functional roles of the protein. A rat yeast artificial chromosome containing Ftz-F1, the gene encoding SF-1, was used to generate mice with different transgenes that varied in size. Rat SF-1 mRNA expression was assayed to assess each transgene's targeting ability. SF-1-deficient/transgene-positive (SF-1(-/-); tg/+) "rescue" mice were then generated and the animals' developmental and reproductive status was evaluated. The results identified differences in expression patterns and rescue abilities that provided insight into SF-1 transcriptional control and function. Comparing transgene maps and mRNA profiles placed critical transcriptional elements for pituitary and hypothalamic expression to a region 3' to intron 4, whereas examination of rescued mice revealed that an approximately 153-kb region of the Ftz-F1 locus recapitulates most or all activity ascribed to the endogenous allele. A second line of rescued mice was hypomorphic, with males showing defects in androgen-dependent tissues due to abnormal Leydig cell differentiation. Histological analysis of embryonic (e14.5) and adult testes from these mice implicated SF-1 in roles that are distinct in fetal and adult Leydig cells.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
NR5A1Humangonadal dysgenesis treatmentISONr5a1 (Rattus norvegicus) RGD 
Nr5a1Ratgonadal dysgenesis treatmentIMP  RGD 
Nr5a1Mousegonadal dysgenesis treatmentISONr5a1 (Rattus norvegicus) RGD 


Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Nr5a1Ratpositive regulation of male gonad development  IMP  RGD 


Genes (Rattus norvegicus)
Nr5a1  (nuclear receptor subfamily 5, group A, member 1)

Genes (Mus musculus)
Nr5a1  (nuclear receptor subfamily 5, group A, member 1)

Genes (Homo sapiens)
NR5A1  (nuclear receptor subfamily 5 group A member 1)