Ppiq12^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ppiq12^C57BL/6J
• Name: prepulse inhibition QTL 12; C57BL/6J
• MGI ID: MGI:6330791
• QTL: Ppiq12 Location: Chr11:101504820-114472363 bp Genetic Position: Chr11, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:276615

Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments.

As a first step toward identifying genes that regulate PPI, the authors performed a QTL screen of PPI phenotypes in a panel of C57BL/6J-Chr^A/J mouse chromosome substitution strains (CSSs). Owing to poor breeding, CSS-13 was unavailable for the study. A total of 1225 mice per CSS were tested over multiple test sessions (average 5.3 sessions for each CSS), and 115 B6 mice were tested across all sessions.

Mice were exposed to six replicate blocks of trials in pseudo-random order. Each block consisted of one pulse-alone trial of a 120 dB 40 milliseconds white noise burst, three trials in which the pulse was preceded by 100 milliseconds by a nonstartling 20-milliseconds prepulse of 70 dB, 75 dB, 80 dB or 85 dB intensities, and one null trial (no stimulus presented).

The authors identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor at least one QTL region that modulates PPI in these CSSs.

The authors performed genetic F2 intercross mapping to identify the PPI locus on chromosome 11 indicated by their finding of significantly elevated PPI in CSS-11 compared with C57BL/6J. F2 intercross mice were generated by mating female CSS-11 mice to male C57BL/6J mice to generate F1 progeny that were heterosomic C57BL/6J and A/J for chromosome 11, followed by brothersister intercrossing. A total of 129 male F2 intercross mice were tested for PPI at 70- to 85-dB prepulse intensities using the same behavioral protocol for PPI as stated above. Mice were genotyped for 49 chromosome 11 SNPs and identification of PPI QTL on chromosome 11 was performed using MAPMAKER/QTL.

Four significant QTL were identified (NCBI Build 37):

QTL Ppiq12 (prepulse inhibition QTL 12) is significant for prepulse inhibition at 70 dB intensity and maps to Chr11:101,475,308 - 114,442,851 (rs29462862 - rs27044905) with a peak LOD score of 2.0 at rs29424603.

QTL Ppiq13 (prepulse inhibition QTL 13) is significant for prepulse inhibition at 75 dB intensity and maps to Chr11:101,475,308 - 114,442,851 (rs29462862 - rs27044905) with a peak LOD score of 4.9 at rs29424603.

QTL Ppiq14 (prepulse inhibition QTL 14) is significant for prepulse inhibition at 80 dB intensity and maps to Chr11:101,475,308 - 114,442,851 (rs29462862 - rs27044905) with a peak LOD score of 4.54 at rs29424603.

QTL Ppiq15 (prepulse inhibition QTL 15) is significant for prepulse inhibition at 85 dB intensity and maps to Chr11:101,475,308 - 114,442,851 (rs29462862 - rs27044905) with a peak LOD score of 4.3 at rs29424603.

Analyses of the PPI data at all four prepulse intensities indicated that the PPI QTL fit a recessive inheritance model in which A/J harbored the high PPI allele.

References

• Original: J:276615 Leussis MP, et al., Genomic survey of prepulse inhibition in mouse chromosome substitution strains. Genes Brain Behav. 2009 Nov;8(8):806-16
• All: 1 reference(s)