Lynf4^O20/A
QTL Variant Detail

Summary

• QTL variant: Lynf4^O20/A
• Name: lymphocyte infiltration 4; O20/A
• MGI ID: MGI:3778978
• QTL: Lynf4 Location: unknown Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: O20/A

Variant description

• Allele Type: QTL
• Inheritance: Recessive

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:128728

Linkage analysis was performed on 197 (OcB-9/Dem x O20/A)F2 animals to identify genetic loci associated with lung tumor lymphocyte infiltration. F2 animals were prenatally exposed to ENU on day 18 of gestation. Lung tumors and lymphocyte infiltration in F2 animals were scored at 16 weeks of age. Parental strain OcB-9/Dem is a recombinant congenic strain derived from O20/A (87.5%) and B10.O20 (12.5%) progenitors. OcB-9/Dem displays a low level of lung tumor lymphocyte infiltration whereas parental strain O20/A displays a high level of infiltration. In human colorectal and ovarian cancers, increased lymphocyte infiltration is associated with better prognosis.

Significant linkage to lymphocyte infiltration, Lynf1, mapped to 67 cM on mouse Chromosome 4 near D4Mit158. This locus was independently confirmed in 35 animals from a (NTX-1 x NTX-16)F2 intercross. (NXT-1 and NXT-16 are recombinant inbred lines derived from OcB-9/Dem and O20/A progenitors.) Lynf1 interacts with Lynf3 on chromosome 6. F2 animals homozygous for B10.O20-derived alleles at both loci display significantly decreased lymphocyte infiltration. Lynf1 maps near several other QTLs: Sluc6 (67 cM), Ltsd4 (67 cM), Marif1 (81.5 cM), and Cinda3 (71 cM).

Lynf2 (lymphocyte infiltration 2) mapped to10 cM on mouse Chromosome 8 near D8Mit3. Homozygosity for O20/A-derived alleles at Lynf2 confers increased lymphocyte infiltration frequency and intensity with an apparently recessive mode of inheritance. This locus interacts with Lynf3 on chromosome 6 (see below). Lynf2 colocalizes with several other QTLs: Sluc20 (10 cM), Ltsd3 (10 cM), Marif2 (19.5 cM), and Cinda5 (15 cM).

On mouse Chromosome 6, Lynf3 (lymphocyte infiltration 3) mapped to 61.2 cM near D6Mit218 and Lynf4 mapped to 35 cM near D6Mit21.Lynf3 interacts with Lynf1 on chromosome 4 and Lynf2 on chromosome 8 by decreasing lymphocyte infiltration. Animals homozygous for B10.O20-derived alleles at Lynf3 and Lynf1, or at Lynf3 and Lynf2, display significantly decreased lymphocyte infiltration.

B10.O20-derived alleles at Lynf4 confer increased lymphocyte infiltration intensity and the mode of inheritance appears dominant. Previously identified QTLs Pgia19 (28 cM), Im4 (34 cM), and Stheal5 (37 cM) map near Lynf4. However, a functional relationship between these loci is unknown.

References

• Original: J:128728 Kakarlapudi N, et al., Control of lymphocyte infiltration of lung tumors in mice by host's genes: mapping of four Lynf (lymphocyte infiltration) loci. Cancer Immunol Immunother. 2008 Feb;57(2):217-25
• All: 1 reference(s)