RGD Reference Report - Tissue-Specific Actions of the Ept1, Ept2, Ept6, and Ept9 Genetic Determinants of Responsiveness to Estrogens in the Female Rat. - Rat Genome Database

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Tissue-Specific Actions of the Ept1, Ept2, Ept6, and Ept9 Genetic Determinants of Responsiveness to Estrogens in the Female Rat.

Authors: Kurz, SG  Hansen, KK  McLaughlin, MT  Shivaswamy, V  Schaffer, BS  Gould, KA  McComb, RD  Meza, JL  Shull, JD 
Citation: Kurz SG, etal., Endocrinology. 2008 Apr 17;.
RGD ID: 2292503
Pubmed: PMID:18420736   (View Abstract at PubMed)
PMCID: PMC2488241   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2008-0173   (Journal Full-text)

Ept1, Ept2, Ept6 and Ept9 are quantitative trait loci (QTL) mapped in crosses between the ACI and Copenhagen (COP) rat strains as genetic determinants of responsiveness of the pituitary gland to estrogens. We have developed four congenic rat strains, each of which carries, on the genetic background of the ACI rat strain, alleles from the COP rat strain that span one of these QTL. Relative to the female ACI rats, female ACI.COP-Ept1 rats exhibited reduced responsiveness to 17beta-estradiol (E2) in the pituitary gland, as evidenced by quantification of pituitary mass and circulating prolactin (PRL), and in the mammary gland, as evidenced by reduced susceptibility to E2-induced mammary cancer. The ACI.COP-Ept2 rat strain exhibited reduced responsiveness to E2 in the pituitary gland, but did not differ from the ACI strain in regard to susceptibility to E2-induced mammary cancer. Interestingly, female Ept2 congenic rats exhibited increased responsiveness to E2 in the thymus, as evidenced by enhanced thymic atrophy. The ACI.COP-Ept6 rat strain exhibited increased responsiveness to E2 in the pituitary gland, which was associated with a qualitative phenotype suggestive of enhanced pituitary vascularization. The ACI.COP-Ept9 rat strain exhibited reduced responsiveness to E2 in the anterior pituitary gland, relative to the ACI rat strain. Neither Ept6 nor Ept9 impacted responsiveness to E2 in the mammary gland or thymus. These data indicate that each of these Ept genetic determinants of estrogen action is unique in regard to the tissues in which it exerts its effects and/or the direction of its effect on estrogen responsiveness.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACI/SegHsdRatBreast Neoplasms MODEL: inducedIAGP17 beta-estradiolcompared to COP/CrCrl controlRGD 
COP/CrCrlRatBreast Neoplasms MODEL: controlIAGP17 beta-estradiol RGD 
ACI.COP-(D10Mgh20-D10Rat4)/ShulRatExperimental Mammary Neoplasms inducedIAGP17 beta-estradiol RGD 
ACI.COP-(D3Mgh16-D3Rat119)/ShulRatExperimental Mammary Neoplasms inducedIAGP17 beta-estradiol RGD 
ACI.COP-(D3Rat130-D3Rat114)/ShulRatExperimental Mammary Neoplasms inducedIAGP17 beta-estradiol RGD 
Emca10RatExperimental Mammary Neoplasms  IAGP E2 induced for 28 weeksRGD 
Ept15RatPituitary Neoplasms  IAGP E2 induced for 12 weeksRGD 
Ept16RatPituitary Neoplasms  IAGP E2 induced for 12 weeksRGD 
Ept17RatPituitary Neoplasms  IAGP E2 induced for 12 weeksRGD 
Ept18RatPituitary Neoplasms  IAGP E2 induced for 12 weeksRGD 
Esta4Ratthymoma  IAGP E2 induced for 12 weeksRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACI.COP-(D3Rat130-D3Rat114)/ShulRatdecreased circulating prolactin level inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
ACI.COP-(D6Rat80-D6Rat146)/ShulRatdecreased circulating prolactin level inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
COP/CrCrlRatdecreased circulating prolactin level inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
Emca10Ratdecreased mammary gland tumor incidence  IDA  RGD 
ACI.COP-(D3Rat130-D3Rat114)/ShulRatdecreased pituitary gland weight inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
COP/CrCrlRatdecreased pituitary gland weight inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
ACI.COP-(D10Mgh20-D10Rat4)/ShulRatdecreased thymus weight  IAGP compared to COP/CrCrl and ACI/SegHsdRGD 
ACI.COP-(D3Mgh16-D3Rat119)/ShulRatdecreased thymus weight  IAGP compared to COP/CrCrlRGD 
ACI.COP-(D6Rat80-D6Rat146)/ShulRatdecreased thymus weight  IAGP17 beta-estradiolcompared to COP/CrCrl and ACI/SegHsdRGD 
ACI/SegHsdRatdecreased thymus weight  IAGP compared to COP/CrCrlRGD 
COP/CrCrlRatdecreased thymus weight inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
ACI.COP-(D6Rat80-D6Rat146)/ShulRatdecreased tumor growth/size inducedIAGP17 beta-estradiolcompared to ACI/SegHsdRGD 
ACI.COP-(D10Mgh20-D10Rat4)/ShulRatincreased circulating prolactin level inducedIAGP17 beta-estradiolcompared COP/CrCrlRGD 
ACI.COP-(D3Mgh16-D3Rat119)/ShulRatincreased circulating prolactin level inducedIAGP17 beta-estradiolcompared to COP/CrCrlRGD 
ACI/SegHsdRatincreased circulating prolactin level inducedIAGP17 beta-estradiolcompared to COP/CrCrlRGD 
ACI/SegHsdRatincreased mammary gland tumor incidence inducedIAGP17 beta-estradiolcompared to ACI.COP-D6Rat80-D6Rat146/Shul��RGD 
ACI.COP-(D10Mgh20-D10Rat4)/ShulRatincreased pituitary gland weight inducedIAGP17 beta-estradiolcompared COP/CrCrlRGD 
ACI.COP-(D3Mgh16-D3Rat119)/ShulRatincreased pituitary gland weight inducedIAGP17 beta-estradiolcompared to ACI/SegHsd and COP/CrCrlRGD 
ACI.COP-(D6Rat80-D6Rat146)/ShulRatincreased pituitary gland weight inducedIAGP17 beta-estradiolcompared to untreated COP/CrCrlRGD 
ACI/SegHsdRatincreased pituitary gland weight inducedIAGP17 beta-estradiolcompared to COP/CrCrlRGD 
ACI.COP-(D3Mgh16-D3Rat119)/ShulRatincreased thymus weight inducedIAGP17 beta-estradiolcompared to COP/CrCrlRGD 
COP/CrCrlRatincreased thymus weight  IAGP compared to ACI/SegHsdRGD 
ACI.COP-(D6Rat80-D6Rat146)/ShulRatincreased tumor latency inducedIAGP17 beta-estradiolcompared to ACI/SegHsd more ...RGD 
Ept15Ratpituitary gland hyperplasia  IDA E2 induced for 12 weeksRGD 
Ept16Ratpituitary gland hyperplasia  IDA E2 induced for 12 weeksRGD 
Ept17Ratpituitary gland hyperplasia  IDA E2 induced for 12 weeksRGD 
Ept18Ratpituitary gland hyperplasia  IDA E2 induced for 12 weeksRGD 
Esta4Ratthymus atrophy  IDA E2 induced for 12 weeksRGD 

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Objects Annotated

QTLs
Emca10  (Estrogen-induced mammary cancer QTL 10)
Ept15  (Estrogen-induced pituitary tumorigenesis QTL 15)
Ept16  (Estrogen-induced pituitary tumorigenesis QTL 16)
Ept17  (Estrogen-induced pituitary tumorigenesis QTL 17)
Ept18  (Estrogen-induced pituitary tumorigenesis QTL 18)
Esta4  (Estrogen-induced thymic atrophy QTL 4)

Objects referenced in this article
QTL Ept1 Estrogen-induced pituitary tumorigenesis QTL 1 Rattus norvegicus
QTL Ept2 Estrogen-induced pituitary tumorigenesis QTL 2 Rattus norvegicus
QTL Ept6 Estrogen-induced pituitary tumorigenesis QTL 6 Rattus norvegicus
QTL Ept9 Estrogen-induced pituitary tumorigenesis QTL 9 Rattus norvegicus

Additional Information