Hipp1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Hipp1^C57BL/6J
• Name: hippocampal weight 1; C57BL/6J
• MGI ID: MGI:2154097
• QTL: Hipp1 Location: unknown Genetic Position: Chr1, cM position of peak correlated region/allele: 74.68 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased hippocampus weight compared to DBA/2J. (J:69261)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:69261

180 F2 animals from reciprocal crosses between inbred strains C57BL/6J and DBA/2J and 35 BXD/Ty (B = C57BL/6J, D = DBA/2J) recombinant inbred (RI) strains were used to identify and confirm QTLs affecting hippocampus weight. Hippocampal weight is 19% greater in progenitor strain C57BL/6J than in progenitor strain DBA/2J. A locus on mouse Chromosome 1, Hipp1, mapped to approximately 83.5 cM near D1Mit145 (LRS = 19.5) in the BXD RI strains and was confirmed with an LRS of 34 in the F2 cross. Hipp1 spans 70 cM - 95 cM on mouse Chromosome 1. Hipp1 maps near Cbm1, a QTL associated with cerebellum weight. Rxrg (retinoid X receptor gamma) and Kcnj9 (potassium inwardly-rectifying channel, subfamily J, member 9) are possible candidates gene for Hipp1. A second locus, Hipp2, mapped to mouse Chromosome 5 at approximately 20 cM near D5Mit352 in the BXD RI strains (LRS = 11.5, suggestive linkage) and confirmed with a maximum LRS of 15.9 in the F2 cross. Hipp2 spans 15 cM - 40 cM on mouse Chromosome 5. Possible candidate genes for Hipp2 included Fgfr3 and gaba receptor genes located at 40 cM on mouse Chromosome 5. C57BL/6J-derived alleles at Hipp1 and Hipp2 appear to increase hippocampal weight in F2 animals. Hipp1 and Hipp2 do not appear to interact.

J:85259

Linkage analysis was performed on 32 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains to identify QTLs associated with hippocampal architecture. The hippocampal volume and body weight of parental strain C57BL/6J is greater compared to the hippocampal volume of DBA/2J. 623 polymorphic loci were analyzed.

Previously identified hippocampus volume QTLs Hipp1 and Hipp2 on mouse Chromosome 1 (89 cM) and mouse chromosome 5 (20 cM), respectively, overlap with suggestive loci detected in this study. The Hipp1 locus overlaps with a locus suggestively linked to pyramidal cell layer volume (LRS=11.1). This interval spans 62 cM - 91 cM. Rxrg is an interesting candidate found in this region.

Grv (granule cell layer volume), mapped to 19 cM on mouse Chromosome 6 with LRS=17.5 near D6Mit207. This locus was identified when Hipp3 was held constant. The QTL interval of Grv spans 7 cM - 30 cM. Hoxa4, Hoxa5, and Npy map to this interval and may be possible candidate genes.

Hipp3 mapped to 31 cM on mouse Chromosome 13. This locus is associated with dentate gyrus volume and exhibits additive inheritance. Hipp3 has a maximum LRS=17.7 near D13Mit94. The QTL interval of Hipp3 spans 26 cM - 45 cM. A strong interaction was observed between Hipp3 and a locus on mouse Chromosome 11 near D11Mit78 (2 cM), which is designated Hipp5. Animals homozygous for C57BL/6J-derived alleles at both Hipp3 and Hipp5 display significantly increased dentate gyrus volume compared to animals of other genotypes.

Hipp4 shows linkage to hippocampal volume and mapped to mouse Chromosome 15 with LRS=15.1. This locus has an additive effect. The Hipp4 interval spans 0 cM to 21 cM. Gdnf and Ghr map to this interval and are possible candidate genes for Hipp4.

Suggestive body weight QTLs mapped to mouse chromosomes 7, 11, and 16. The chromosome 11 body weight QTL does not overlap with the Grv. Suggestive brain weight QTLs mapped to mouse Chromosomes 15, 16, and 19.

References

• Original: J:69261 Lu L, et al., Complex trait analysis of the hippocampus: mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice. J Neurosci. 2001 May 15;21(10):3503-14
• All: 1 reference(s)