Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight.
To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase reporter gene. Staining for beta-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P < 0.01) on a rotating rod than do wt littermates. We have also noted a lower body weight gain (P < 0.05) in Foxs1beta-gal/lbeta-gal males on a high-fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.
Heglind
Mikael
M
Medical Genetics, Department of Medical Biochemistry, Göteborg University, Medicinareg. 9A, Box 440, SE 405 30 Göteborg, Sweden.
Cederberg
Anna
A
Aquino
Jorge
J
Lucas
Guilherme
G
Ernfors
Patrik
P
Enerbäck
Sven
S
D000818:Animals; D001835:Body Weight / Q000235:genetics* / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics* / Q000502:physiology; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012399:Rotation; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D051858:Forkhead Transcription Factors; C502463:Foxs1 protein, mouse; D014157:Transcription Factors; D001616:beta-Galactosidase