Meeting Abstract
Fibroblast growth factors (Fgfs) are a family of 22 cytokines that bind to 4 receptors, many of which play a critical role in cortical development. Fgf ligands, including Fgf2, and the Fgfr1 and Fgfr2 receptors are expressed by astrocytes and astrocytic stem cell lineages of the developing and adult CNS. Previous studies have shown that Fgfrs can have compensatory effects on proliferation and development. We have inactivated Fgfr1 and Fgfr2 in postnatal astrocytes by tamoxifen inducible Cre mediated recombination using the hGFAP-CreERT2 (GCE) transgene. We targeted postnatal astrocytes by administering injections of tamoxifen from P14-17, 60 mg/kg i.p. We tested locomotor behavior of the mice for 30 minutes in an open field. Male double KO mice showed hypoactivity compared to male control littermates with total time immobile having a p-value of .0380. Other trends were less distance travelled (p=.0542), lower mean speed (.0567), and more total mobile episodes (0521) possibly indicating that the animals began more movements but were slower and spent more time resting. We observed no differences in anxiety behaviors on the elevated plus maze test, and no differences in memory were observed in the 1-day morris water maze. It was previously shown that Fgfr1 and Fgfr2 double KO starting at E13.5 lead to multiple cerebellar abnormalities. The locomotor behavior findings lead us to hypothesize that there may be a postnatal cerebellar defect in Fgfr1/Fgfr2 double KO mice. We compared control and Fgfr1/Fgfr2 double KO mice on a hindlimb clasping test. We found double KO mice had significantly higher scores on this test (p=.05), indicating an impairment in motor coordination. Future work will examine cerebellar morphology. We will compare the effects of Fgfr1 single and Fgfr1/Fgfr2 double mutants upon PV neuron maturation, and postnatal hippocampal proliferation.
