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Published on: October 21, 2015
Prokr2-deficient mice display vascular dysmorphology of the fetal testes: potential implications for Kallmann
T Svingen1, K S McClelland, K Masumoto
1Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
Abstract:
Kallmann syndrome is a form of hypogonadotropic hypogonadism also associated with the loss of smell. It is a phenotypically and genetically heterogeneous disorder, with mutations in several known causative genes now accounting for approximately 30% of cases. The prevalence for the disease is also much higher in males than in females, a phenomenon that remains to be fully explained. Here, we show that loss of Prokr2, which is linked to autosomal recessive Kallmann syndrome type 3 (KAL3; OMIM 244200), affects fetal testis differentiation in mice. We find that Prokr2 is specifically expressed in the XY gonads during sex determination and fetal sexual differentiation, and knockout mice display a variable degree of compromised vasculature in the fetal testes. This phenotype offers potential insight into the clinical heterogeneity observed within familial cases, and may contribute to the gender bias in Kallmann syndrome patients.
Insights
Loss of Prokr2 impacts fetal testis development in mice, potentially explaining clinical variations and the higher prevalence of Kallmann syndrome in males. This research sheds light on hypogonadotropic hypogonadism.
Area of Science:
- Reproductive biology
- Developmental biology
- Genetics
Background:
- Kallmann syndrome is a congenital disorder characterized by hypogonadotropic hypogonadism and anosmia.
- Genetic mutations explain about 30% of Kallmann syndrome cases, with a higher incidence in males.
- The genetic and molecular underpinnings of Kallmann syndrome's heterogeneity and gender bias require further elucidation.
Purpose of the Study:
- To investigate the role of Prokr2 in fetal testis differentiation.
- To explore the potential contribution of Prokr2 to Kallmann syndrome's clinical variability and male predominance.
Main Methods:
- Utilized a mouse model with a knockout of the Prokr2 gene.
- Examined Prokr2 expression patterns in XY gonads during critical developmental stages.
- Assessed fetal testis vasculature and differentiation in Prokr2 knockout mice.
Main Results:
- Prokr2 is expressed in XY gonads during sex determination and fetal sexual differentiation.
- Prokr2 knockout mice exhibited compromised fetal testis vasculature.
- Observed variable phenotypes in knockout mice, suggesting a role in clinical heterogeneity.
Conclusions:
- Loss of Prokr2 function disrupts fetal testis development and vasculature.
- This disruption may contribute to the observed clinical heterogeneity in Kallmann syndrome.
- The findings suggest a potential mechanism for the male bias in Kallmann syndrome prevalence.
