Gender Differences, Hormones and Sex Chromosomes Poster Presentation

P1142 - “The contribution of sex hormones to disease incidence and phenotype in the spontaneous TCR1640 mouse model.” (ID 1487)

Speakers
  • M. Mercier
Authors
  • R. Rébillard
  • S. Larouche
  • O. Tastet
  • C. Grasmuck
  • C. Hoornaert
  • L. Bourbonniere
  • A. Prat
Presentation Number
P1142
Presentation Topic
Gender Differences, Hormones and Sex Chromosomes

Abstract

Background

TCR1640 transgenic mice, a model of spontaneous experimental autoimmune encephalomyelitis (EAE), are a powerful tool to study the sexual dimorphism seen in MS patients. Being at higher risk of developing EAE, TCR1640 females develop a relapsing-remitting (RR) disease course while male TCR1640 develop mostly a primary progressive (PP) form. Clinical observations in MS patients and other EAE models suggest a potentially protective role of sex hormones but their contribution to disease development remains to be elucidated.

Objectives

We aim to characterize the role of sex hormones, in both sexes, on multiple aspects of the MS course including disease incidence, phenotype and severity in a unique and relevant mouse model.

Methods

Gonadectomies have been performed on TCR1640 mice between 21-28 days postnatal, before onset of puberty (n= 22 males, n= 25 females). These mice, as well as sham control mice (n= 17 males, n= 21 females), were scored daily for signs of paralysis and ataxia and were followed up for >150 days.

Results

For both male and female TCR1640 mice, gonadectomy seems to affect disease incidence. Absence of sex hormones in males display a major protective role on the disease 75 days after surgery whereas the protective effect of female sex hormones becomes apparent ~90 days after surgery. Not only there are fewer male and females sham mice that do fall ill in theses period, but mice that do fall ill do so with delayed onset compared to their gonadectomized littermates. Preliminary results show that gonadectomy does not seem to affect disease phenotype for either sex. More advanced bioinformatical analysis will now be used to define different phenotype clusters based on EAE score evolution, allowing us to zoom in on the potential influence of sex hormones on each of these different phenotypes.

Conclusions

We have demonstrated that both male and female sex hormones have a potential protective role in the TCR1640 model, appearing to decrease disease incidence as well as delaying disease onset. Sex hormones however do not seem to control disease phenotype, strongly suggesting that the sexual dichotomy seen in clinical disease course is dictated by sex chromosomes rather than sex hormones.

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