CD19 maps to a region of conservation between human chromosome 16 and mouse chromosome 7

Ord, David C.; Edelhoff, Susanne; Dushkin, Holly; Zhou, Liang; Beier, David R.; Tedder, Thomas F.

doi:10.1007/bf00189228

Cited by 6 publications

(1 citation statement)

References 30 publications

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“…The CD11 genes are candidate modifier loci because of their known subunit interaction with CD18, and in humans the CD11 genes map to a small region of chromosome 16 (13). Although only the mouse CD1la gene has been mapped (chromosome 7), it is likely that the other CD11 genes will also map to this region (14,15). If either locus was the primary modifier, we would predict that all diseased mice would be homozygous for the PL/J genotype and all nondiseased mice would be heterozygous for the PL/J and C57BL/6 alleles.…”

Section: Methodsmentioning

confidence: 99%

A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

Bullard

Scharffetter‐Kochanek

McArthur

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

107

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Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and the development of scales and crusts. The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders. Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J)F1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as few as one), in addition to CD18, determine susceptibility to the disorder. This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the 82 integrins in inflammatory processes.A large number of leukocyte and endothelial cell adhesion molecules are known to play a role in inflammatory processes, leukocyte trafficking, and immune responses (1). The molecules include immunoglobulin family members such as intercellular adhesion molecule 1 (ICAM-1), the selectins, selectin ligands, and leukocyte integrins (1). The P2 leukocyte integrins are heterodimers of CD18 with one of three CD11 subunits:LFA-1 (CD18/CD11a), Mac-1 (CD18/CD11b), and p150/95 (CD18/CD11c). Mutations in CD18 have been reported in humans (2, 3) and in cattle (4, 5) and result in the lifethreatening disorder termed leukocyte adhesion deficiency type I. CD18-deficient patients suffer from recurrent microbial infections, leukocytosis, impaired wound healing, failure of granulocyte -emigration, and lack of pus formation (2, 3). Severe and moderate phenotypes have been described in humans, and the severity of the phenotype appears to correlate with the presence of null or hypomorphic mutations, respectively (3, 6).Previously, a hypomorphic mutation for CD18 was introduced into mice with homozygotes displaying mild leukocytosis, an impaired response to chemically induced peritonitis, and delays in transplantation rejection (7). These mice express a low level of normal CD18 on leukocytes with 2-16% ofThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.wild-type levels of CD18 expression on resting or activated leukocytes...

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Section: Methodsmentioning

confidence: 99%