Identification of collagen-induced arthritis loci in aged multiparous female mice

The similarities between rheumatoid arthritis (RA) in man and collagen-induced arthritis (CIA) in mice are well established, although differences in the disease pattern exist [1-3]. Characteristic of RA is the fact that women of reproductive age are more susceptible to the disease than men [4]. It has also been reported that 75% of female patients (23 out of 31 females) with RA exhibit clinical remission during the course of pregnancy [5]. On the other hand, it has been suggested that the onset of RA is postponed by parity. The risk of onset is reduced during pregnancy, while in the first year postpartum the chance of onset is increased [6,7]. The results of a recent study of RA in women, however, indicate that pregnancy history does not increase the incidence of the disease later in life [8].Adequate animal models are useful tools for the identification of genes involved in complex human diseases. CIA in mice shares both immunological and pathological characteristics with human RA and is one of the most used models for the identification of genes and mechanisms involved in arthritis. The incidence of CIA is sex dependent, like the incidence in RA, although different species and different variants of the disease could lead to both male and female predominance. Male mice are more often affected than females. Gender differences in CIA susceptibility are dependent on many factors, including genetic, hormonal and behavioral influences [9]. However, isolated factors are remarkably consistent between RA and the different animal models [3,9]. Pregnancy in mice, like pregnancy in women, normally causes remission of arthritis [5,10], while exacerbation often occurs postpartum [7,10,11]. Pregnancy-induced remission of CIA in mice appears to be caused by the increase in estrogen levels, while the postpartum exacerbation can be explained by the dramatic drop in estrogen [10], possibly together with increased prolactin levels [11]. To what extent the pregnancy history (parity) a