Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis).
We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads to significantly reduced serum stimulation of fra-1 expression in gene targeted mouse fibroblasts, demonstrating that mitogen induction of fra-1 is partially mediated by c-Fos/AP-1. A polymorphic (CA)n microsatellite marker was found in intron 2 of fra-1 and used to map the gene to the centromeric region of mouse chromosome 19. Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene for oc. The segregation of fra-1 in two different crosses of mice carrying oc and an allelism test between oc and a targeted disruption of fra-1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.
Schreiber
M
M
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Poirier
C
C
Franchi
A
A
Kurzbauer
R
R
Guenet
J L
JL
Carle
G F
GF
Wagner
E F
EF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D005091:Exons; D015870:Gene Expression; D005796:Genes; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010026:Osteosclerosis / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014018:Tissue Distribution; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000099169:Fos-Related Antigen 1