In addition to CRF-BP transgenic models, a CRF-BP KO mouse was created by targeted gene deletion (Karolyi et al., 1999). These mice would be expected to exhibit overactive CRF pathways, given the lack of a CRF depot. Although no obvious changes in baseline or stress-induced HPA hormones were seen, CRF-BP KO mice display a modest increase in anxiety-related behavior. In addition, CRF-BP KO mice showed alterations in feeding behavior. Male CRF-BP KO mice ate less during the light and dark cycles and did not gain weight as rapidly as WT males (Karolyi et al, 1999). These findings complement those observed with mMT-CRF-BP mice wherein increased weight gain accompanied global excess of CRF-BP (Lovejoy et al, 1998).
Collectively, CRF-BP transgenic and KO models suggest that CRF-BP may be important in regulating behavioral effects of CRF/urocortin 1, yet plays a minor role in HPA axis homeostasis. That food intake was altered in these models despite normal feeding behavior in CRF KO mice, strongly suggests that these effects of CRF-BP may be mediated through an alternate ligand, such as urocortin 1. These models demonstrate that HPA axis and central CRF pathways are regulated independently. Furthermore, when regulatory components are altered, the HPA axis seems to be exquisitely capable of readjusting setpoints in order to maintain allostasis.
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