Macdonald, Katie E. (Katie Elizabeth) (2011) A novel mouse model for partial androgen insensitivity syndrome. Masters thesis, Memorial University of Newfoundland.
- Accepted Version
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Androgen 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.
|Item Type:||Thesis (Masters)|
|Additional Information:||Bibliography: leaves 104-110.|
|Department(s):||Medicine, Faculty of|
|Library of Congress Subject Heading:||Androgens--Pathophysiology; Karyotypes--Animal models; Mice--Anatomy|
|Medical Subject Heading:||Androgens; Karyotype; Mice--anatomy & histology; Models, Animal|
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