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Memorial University - Electronic Theses and Dissertations 5
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Document Description
TitleA novel mouse model for partial androgen insensitivity syndrome
AuthorMacdonald, Katie E. (Katie Elizabeth), 1984-
DescriptionThesis (M.Sc.)--Memorial University of Newfoundland, 2011. Medicine
Date2011
Paginationxiii, 112 leaves : ill. (some col.).
SubjectAndrogens--Pathophysiology; Karyotypes--Animal models; Mice--Anatomy
DegreeM.Sc.
Degree GrantorMemorial University of Newfoundland. Faculty of Medicine
DisciplineMedicine
LanguageEng
NotesBibliography: leaves 104-110.
AbstractAndrogen Insensitivity Syndrome (AIS) is the under-masculinization of individuals with XY sex chromosome karyotypes. A broad clinical spectrum of AIS exists, from mild to partial to complete AIS. Mouse models of complete AIS have been used to study aspects of sexual development, physiology, and behavioural outcomes in the absence of androgenic signaling. There is currently no animal model of partial AIS (PAIS), and the novel mouse strain described in this research satisfies the clinical description of human PAIS patients, appearing outwardly male with additional feminine characteristics. My research on the PAIS mouse model focuses on the anatomical features and endocrinology of this unique strain, and the role of partial androgen signaling as a cause of behavioural anxiety. -- Anatomically, PAIS male mice have similar body size and weight to wild-type (WT) males, but they have an intermediate anal-genital distance that is shorter than WT males, but longer than WT female mice. The PAIS males do possess intra-abdominal testes, but they are infertile, as they lack internal reproductive structures such as the seminal vesicles, prostate, epididymis and vas deferens. Androgen-responsive organs are significantly smaller in mature PAIS males compared to age-matched WT males, including the testes, preputial glands and kidneys; however, this phenotype did not correlate with a lack of testosterone (T) synthesis, since T concentrations were not different between WT and PAIS males as juveniles (30 d) or young adults (50 d). Following an androgen sensitivity test, androgen-responsive growth of the preputial glands in castrated males was significantly reduced in T-supplemented PAIS versus WT males, indicating partial androgen insensitivity. A defect in androgen sensitivity was further indicated by the elevated serum gonadotropin concentrations at 30 d of age (follicle stimulating hormone (FSH)) and 50 d of age (FSH and luteinizing hormone (LH)), suggesting a failure of negative feedback regulation at the level of the hypothalamic-anterior pituitary-gonadal (HPG) axis. Behaviourally, the PAIS mutation significantly decreased male-typical behaviours (aggression and sexual interest) and increased anxiety-like behaviour in a standard paradigm for measurement of rodent anxiety - the elevated plus maze. One assay of social behaviour showed no difference in social interactions between PAIS and WT male mice. This novel rodent model of PAIS satisfies the criteria for human PAIS patients, and will serve as an excellent tool to further explore the potential consequences of PAIS to male health.
TypeText
Resource TypeElectronic thesis or dissertation
FormatImage/jpeg; Application/pdf
SourcePaper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
RightsThe author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
CollectionElectronic Theses and Dissertations
Scanning StatusCompleted
PDF File(3.40 MB) -- http://collections.mun.ca/PDFs/theses/Macdonald_KatieElizabeth.pdf
CONTENTdm file name22663.cpd