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CD-1 is the outbred mouse line most often used in toxicology and carcinogenicity bioassays. A literature survey revealed a relatively high (21.8%) incidence of spontaneous lung tumors in these mice, and a susceptibility to lung tumorigenesis induced by vinyl chloride, styrene or benzene inhalation that is not seen in B6C3F1 or C57BL/6 mice, or in rats and hamsters. As the pulmonary adenoma susceptibility 1 (Pas1) locus is the major determinant of genetic susceptibility to lung tumorigenesis in mice, we analyzed CD-1 mice for genetic polymorphisms of the Kras2 and Pthlh genes, which are tightly linked with the Pas1 locus. From 95 to 98% of CD-1 mice carried the susceptibility allele at the Pas1 locus either at homozygosity or heterozygosity, providing a molecular genetic explanation for the high susceptibility of CD-1 mice to spontaneous and chemically induced lung tumorigenesis. These results may have implications for the risk assessment of chemicals in humans using experimental animals that display strain-specific lung tumorigenicity.

Lung tumor susceptibility in inbred mouse strains is caused by the susceptibility allele at the pulmonary adenoma susceptibility 1 (Pas1^s) locus. However, after urethane treatment, most strains carrying the Pas1^s allele show an intermediate (1–4 tumors/mouse) instead of a highly susceptible (15–30 tumors/mouse) lung tumor phenotype. To test the hypothesis that strains displaying the intermediate lung tumor phenotype carry dominant or codominant resistance alleles at pulmonary adenoma resistance (Par) loci, we crossed mice of intermediate susceptibility or resistance to lung tumorigenesis with the highly susceptible A/J strain. Eleven F1 hybrids were treated with urethane to induce lung tumorigenesis. The A/J strain developed 35.3 tumors/mouse, while its F1 hybrid with C57BL/6J mice (null allele at Par loci) developed 22.8 tumors/mouse due to the Pas1 allele dosage effect. F1 hybrids of strains 129/SvJ, CBA/J, ST/J and LP/J (Pas1^s) and of SPW, DBA/2J and C57L/J (Pas1^r) mice showed significant reduction in lung tumor multiplicity (i.e., 0.3–12.8 tumors/mouse) compared to A/J and (A/J × C57BL/6J)F1 mice. These results indicate that resistance alleles at Par loci are common in inbred mouse strains and account for the lung tumorigenesis intermediate phenotype of strains carrying the Pas1^s allele. © 2002 Wiley-Liss, Inc.

Nonspecific X-linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X-linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2–26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. © 2001 Wiley-Liss, Inc.