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Evidence for genes controlling resistance to Heligmosomoides bakeri on mouse chromosome 1

Published online by Cambridge University Press:  07 November 2014

HARRY NOYES ,
JOHN GITHIORI ,
JAN E. BRADLEY ,
STEVE KEMP  and
JERZY M. BEHNKE
HARRY NOYES
Affiliation:
Institute of Integrative Biology, Biosciences Building, University of Liverpool Crown Street, Liverpool L69 7ZB, UK
JOHN GITHIORI
Affiliation:
International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, Kenya
JAN E. BRADLEY
Affiliation:
School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
STEVE KEMP
Affiliation:
International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, Kenya
JERZY M. BEHNKE*
Affiliation:
School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
*
*Corresponding author: School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK. E-mail: jerzy.behnke@nottingham.ac.uk
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Summary

Resistance to infections with Heligmosomoides bakeri is associated with a significant quantitative trait locus (QTL–Hbnr1) on mouse chromosome 1 (MMU1). We exploited recombinant mice, with a segment of MMU1 from susceptible C57Bl/10 mice introgressed onto MMU1 in intermediate responder NOD mice (strains 1094 and 6109). BALB/c (intermediate responder) and C57Bl/6 mice (poor responder) were included as control strains and strain 1098 (B10 alleles on MMU3) as NOD controls. BALB/c mice resisted infection rapidly and C57Bl/6 accumulated heavy worm burdens. Fecal egg counts dropped by weeks 10–11 in strain 1098, but strains 1094 and 6109 continued to produce eggs, harbouring more worms when autopsied (day 77). PubMed search identified 3 genes (Ctla4, Cd28, Icos) as associated with ‘Heligmosomoides’ in the B10 insert. Single nucleotide polymorphism (SNP) differences in Ctla4 could be responsible for regulatory changes in gene function, and a SNP within a splice site in Cd28 could have an impact on function, but no polymorphisms with predicted effects on function were found in Icos. Therefore, one or more genes encoded in the B10 insert into NOD mice contribute to the response phenotype, narrowing down the search for genes underlying the H. bakeri resistance QTL, and suggest Cd28 and Ctla4 as candidate genes.

Keywords

Heligmosomoides polygyrus bakeriNOD miceCtla4IcosCd28C57BL/10resistance QTLworm burdensfecal egg counts
Type
Research Article
Information
Parasitology , Volume 142 , Issue 4 , April 2015 , pp. 566 - 575
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Copyright
Copyright © Cambridge University Press 2014 

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Footnotes

† Current address: Kemet Company, P.O. Box 39099-00623, Nairobi, Kenya.

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