Date of Award

Spring 1-1-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Integrative Physiology

First Advisor

Pei-San Tsai

Second Advisor

David Norris

Third Advisor

Robert Spencer

Abstract

Fibroblast growth factor receptor 1 (Fgfr1) gene mutations can cause deficiencies in gonadotropin-releasing hormone (GnRH) production in humans. GnRH deficiencies cause Kallmann syndrome and a form of hypogonadotropic hypogonadism. Fgfr1 deficiencies in mice have led to several abnormalities associated with reproduction including a reduction in neurons that produce GnRH. Fgfr1 global deletion causes widespread disruptions in development. The goal of this thesis was to use a Cre-loxP strategy to produce transgenic mice with conditional Fgfr1 deletion in GnRH neurons. These transgenic mice will be used to investigate if Fgfr1 has a cell-autonomous effect on GnRH neurons. Mice were generated using male GnRH-Cre mice (GnRH-Cre+/-) breed with female mice with floxed Fgfr1 exon 4 allele (Fgfr1flox/flox). After two generations, male and female conditional knockout (KO) mice (GnRH-Cre+/-: Fgfr1flox/flox) and control mice (GnRH-Cre-/-: Fgfr1flox/flox) were produced. To investigate deficiencies in the conditional KO mice, the reproductive phenotype was assessed measuring GnRH neurons, luteinizing hormone (LH) levels, and reproductive measurements. Results from this experiment show no significant differences in GnRH neurons or LH plasma concentration levels. However, significant deficiencies are found in the reproductive capabilities of the conditional KO mice. These results suggest that conditional KO mice in both sexes have functionally compromised GnRH neurons despite normal GnRH neuronal populations. However, the female reproductive axis of the conditional KO mice demonstrates greater reproductive impairments when compared to male conditional KO mice. The overall findings of this thesis work illustrate that Fgfr1 does have a direct effect on GnRH neuronal function without causing an alteration to GnRH neuronal numbers.

Included in

Endocrinology Commons

Share

COinS