Sequence-based characterization of structural variation in the mouse genome

Yalcin, Binnaz; Wong, Kim; Agam, Avigail; Goodson, Martin; Keane, Thomas M.; Gan, Xiangchao; Nellåker, Christoffer; Goodstadt, Leo; Nicod, Jérôme; Bhomra, Amarjit; Hernandez-Pliego, Polinka; Whitley, Helen; Cleak, James; Dutton, Rebekah; Janowitz, Deborah; Mott, Richard; Adams, David J.; Flint, Jonathan

doi:10.1038/nature10432

Cited by 288 publications

(360 citation statements)

References 30 publications

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“…The D2 strain possesses a non-synonymous allelic variant of the Taar1 gene (Sanger Mouse Genomes Project SNP browser, 2014; Keane et al, 2011;Yalcin et al, 2011), as compared with the reference B6 strain. To date, the SNP (C229A) is reported to be unique to the D2 strain; the reference B6 allele is shared by at least 27 additional strains.…”

Section: Taar1 Sequencementioning

confidence: 99%

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Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Harkness

Shi

Janowsky

et al. 2015

Neuropsychopharmacol

149

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Continued methamphetamine (MA) use is dependent on a positive MA experience and is likely attenuated by sensitivity to the aversive effects of MA. Bidirectional selective breeding of mice for high (MAHDR) or low (MALDR) voluntary consumption of MA demonstrates a genetic influence on MA intake. Quantitative trait locus (QTL) mapping identified a QTL on mouse chromosome 10 that accounts for greater than 50% of the genetically-determined differences in MA intake in the MAHDR and MALDR lines. The trace amine-associated receptor 1 gene (Taar1) is within the confidence interval of the QTL and encodes a receptor (TAAR1) that modulates monoamine neurotransmission and at which MA serves as an agonist. We demonstrate the existence of a non-functional allele of Taar1 in the DBA/2J mouse strain, one of the founder strains of the selected lines, and show that this non-functional allele co-segregates with high MA drinking and with reduced sensitivity to MA-induced conditioned taste aversion (CTA) and hypothermia. The functional Taar1 allele, derived from the other founder strain, C57BL/6J, segregates with low MA drinking and heightened sensitivity to MA-induced CTA and hypothermia. A role for TAAR1 in these phenotypes is corroborated in Taar1 transgenic mice: Taar1 knockout mice consume more MA and exhibit insensitivity to MA-induced CTA and hypothermia, compared with Taar1 wild-type mice. These are the first data to show that voluntary MA consumption is, in part, regulated by TAAR1 function. Behavioral and physiological studies indicate that TAAR1 function increases sensitivity to aversive effects of MA, and may thereby protect against MA use.

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Section: Taar1 Sequencementioning

confidence: 99%

“…DBA/2J (D2) mice possess a unique non-synonymous single-nucleotide polymorphism (SNP, C229A) in Taar1 (Sanger Mouse Genomes Project SNP browser, 2014; Keane et al, 2011;Yalcin et al, 2011) that is not present in C57BL/6J (B6) mice. These are the two progenitor strains of the MADR lines.…”

Section: Introductionmentioning

confidence: 99%

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Harkness

Shi

Janowsky

et al. 2015

Neuropsychopharmacol

149

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“…Many of them result in significant tissue-specific expression bias and phenotypic variation. 10,11 C57BL/6J mice are susceptible to high-fat diet-induced type 2 diabetes. 12 JF1 mice are especially sensitive to high-fat diet-induced diabetes and obesity, whereas MSM/Ms mice are resistant.…”

Section: Introductionmentioning

confidence: 99%

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Shen

Shi

Suzuki

et al. 2016

Laboratory Investigation

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Retinol-binding protein 4 (RBP4) is a specific carrier for retinol in the blood. In hepatocytes, newly synthesized RBP4 associates with retinol and transthyretin and is secreted into the blood. The ternary transthyretin-RBP4-retinol complex transports retinol in the circulation and delivers it to target tissues. Rbp4-deficient mice in a mixed genetic background (129xC57BL/6J) have decreased sensitivity to light in the b-wave amplitude on electroretinogram. Sensitivity progressively improves and approaches that of wild-type mice at 24 weeks of age. In the present study, we produced Rbp4-deficient mice in the C57BL/6 genetic background. These mice displayed more severe phenotypes. They had decreased a-and b-wave amplitudes on electroretinograms. In accordance with these abnormalities, we found structural changes in these mice, such as loss of the peripheral choroid and photoreceptor layer in the peripheral retinas. In the central retinas, the distance between the inner limiting membrane and the outer plexiform layer was much shorter with fewer ganglion cells and fewer synapses in the inner plexiform layer. Furthermore, ocular developmental defects of retinal depigmentation, optic disc abnormality, and persistent hyaloid artery were also observed. All these abnormalities had not recovered even at 40 weeks of age. Our Rbp4-deficient mice accumulated retinol in the liver but it was undetectable in the serum, indicating an inverse relation between serum and liver retinol levels. Our results suggest that RBP4 is critical for the mobilization of retinol from hepatic storage pools, and that such mobilization is necessary for ocular development and visual function.

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“…The CC is composed of a panel of recombinant inbred lines derived from eight-way crosses using five classical inbred strains (C57BL/6J, 129S1/SvImJ, A/J, NOD/ShiLtJ, NZO/HlLtJ) and three wild-derived inbred strains (WSB/EiJ, PWK/PhJ, and CAST/EiJ) (Collaborative Cross Consortium 2012). The genomes of the CC founder strains Yalcin et al 2011) and the features of the CC population have been described recently (Collaborative Cross Consortium 2012). Results obtained using incipient CC lines that were partially inbred (referred to as "preCC" mice) have been notable in terms of phenotypic diversity and identification of new QTL (Aylor et al 2011;Bottomly et al 2012;Kelada et al 2012;Ferris et al 2013;Kelada et al 2014).…”

mentioning

confidence: 99%

Genetic Regulation ofZfp30, CXCL1, and Neutrophilic Inflammation in Murine Lung

et al. 2014

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Allergic asthma is a complex disease characterized in part by granulocytic inflammation of the airways. In addition to eosinophils, neutrophils (PMN) are also present, particularly in cases of severe asthma. We sought to identify the genetic determinants of neutrophilic inflammation in a mouse model of house dust mite (HDM)-induced asthma. We applied an HDM model of allergic asthma to the eight founder strains of the Collaborative Cross (CC) and 151 incipient lines of the CC (preCC). Lung lavage fluid was analyzed for PMN count and the concentration of CXCL1, a hallmark PMN chemokine. PMN and CXCL1 were strongly correlated in preCC mice. We used quantitative trait locus (QTL) mapping to identify three variants affecting PMN, one of which colocalized with a QTL for CXCL1 on chromosome (Chr) 7. We used lung eQTL data to implicate a variant in the gene Zfp30 in the CXCL1/PMN response. This genetic variant regulates both CXCL1 and PMN by altering Zfp30 expression, and we model the relationships between the QTL and these three endophenotypes. We show that Zfp30 is expressed in airway epithelia in the normal mouse lung and that altering Zfp30 expression in vitro affects CXCL1 responses to an immune stimulus. Our results provide strong evidence that Zfp30 is a novel regulator of neutrophilic airway inflammation.

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Sequence-based characterization of structural variation in the mouse genome

Cited by 288 publications

References 30 publications

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Genetic Regulation ofZfp30, CXCL1, and Neutrophilic Inflammation in Murine Lung

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