Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory 
disorder that primarily affects bone but is often accompanied by inflammation of 
the skin and/or gastrointestinal tract. The etiology is unknown but evidence 
suggests a genetic component to disease susceptibility. Although most cases of 
CRMO are sporadic, there is an autosomal recessive syndromic form of the 
disease, called Majeed syndrome, which is due to homozygous mutations in LPIN2. 
In addition, there is a phenotypically similar mouse, called cmo (chronic 
multifocal osteomyelitis) in which the disease is inherited as an autosomal 
recessive disorder. The cmo locus has been mapped to murine chromosome 18. In 
this report, we describe phenotypic abnormalities in the cmo mouse that include 
bone, cartilage and skin inflammation. Utilizing a backcross breeding strategy, 
we refined the cmo locus to a 1.3 Mb region on murine chromosome 18. Within the 
refined region was the gene pstpip2, which shares significant sequence homology 
to the PSTPIP1. Mutations in PSTPIP1 have been shown to cause the 
autoinflammatory disorder PAPA syndrome (pyogenic arthritis, pyoderma 
gangrenosum and acne). Mutation analysis, utilizing direct sequencing, revealed 
a single base pair change c.293T --> C in the pstpip2 gene resulting in a highly 
conserved leucine at amino acid 98 being replaced by a proline (L98P). No other 
mutations were found in the coding sequence of the remaining genes in the 
refined interval, although a 50 kb gap remains unexplored. These data suggest 
that mutations in pstpip2 may be the genetic explanation for the 
autoinflammatory phenotype seen in the cmo mouse.