Digit ratio (2Dratio4D) differences between 20 strains of inbred mice.

The second to fourth digit ratio (2Dratio4D) is sexually differentiated in a variety of species, including humans, rats, birds, and lizards. In humans, this ratio tends to be lower in males than in females. Lower digit ratios are believed to indicate increased prenatal testosterone exposure, and are associated with more masculinized behavior across a range of traits. The story seems more complicated in laboratory mice. We have previously shown that there is no sex difference in the digit ratios of inbred mice, but found behavioral evidence to suggest that higher 2Dratio4D is associated with more masculinized behaviors. Work examining intrauterine position effects show that neighbouring males raise pup digit ratio, suggesting again that higher digit ratios are associated with increased developmental androgens. Other work has suggested that masculinization is associated with lower digit ratios in lab mice. Here, we examine the fore- and hindlimb digit ratios of 20 inbred mouse strains. We find large inter-strain differences, but no sexual dimorphism. Digit ratios also did not correlate with mice behavioral traits. This result calls into question the use of this trait as a broadly applicable indicator for prenatal androgen exposure. We suggest that the inbred mice model presents an opportunity for researchers to investigate the genetic, and gene-environmental influence on the development of digit ratios.

Selective breeding for a behavioral trait changes digit ratio.

The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D:4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D:4D ratio is lower (i.e. more "masculinized") in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D:4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D:4D. This apparent "feminization" in mice is opposite to the relationship seen between 2D:4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D:4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes.

Gauging recovery after hemorrhagic stroke in rats: implications for cytoprotection studies.

Successful clinical translation of prospective cytoprotectants will likely occur only with treatments that improve functional recovery in preclinical (rodent) studies. Despite this assumption, many rely solely on histopathologic end points or the use of one or two simple behavioral tests. Presently, we used a battery of tests to gauge recovery after a unilateral intracerebral hemorrhagic stroke (ICH) targeting the striatum. In total, 60 rats (N=15 per group) were stereotaxically infused with 0 (SHAM), 0.06 (MILD lesion), 0.12 (MODERATE lesion), or 0.18 U (SEVERE lesion) of bacterial collagenase. This created a range of injury akin to moderate (from SEVERE to MODERATE or MODERATE to MILD lesion size approximately 30% reduction) and substantial cytoprotection (SEVERE to MILD lesion size--51% reduction). Post-ICH functional testing occurred over 30 days. Tests included the horizontal ladder and elevated beam tests, swimming, limb-use asymmetry (cylinder) test, a Neurologic Deficit Scale, an adhesive tape removal test of sensory neglect, and the staircase and single pellet tests of skilled reaching. Most tests detected significant impairments (versus SHAM), but only a few (e.g., staircase) frequently distinguished among ICH groups and none consistently differentiated among all ICH groups. However, by using a battery of tests we could behaviorally distinguish groups. Thus, preclinical testing would benefit from using a battery of behavioral tests as anything less may miss treatment effects. Such testing must be based on factors including the type of lesion, the postoperative delay and the time required to complete testing.