Evaluation of neurological mouse mutants caused by ENU mutagenesis by Isaacs, A, Potter, A, Masih, M, Vizor, L, Oliver, P, Davies, K, Peters, J, Nolan, P, Martin, J, Walsh, F, Brown, S, Hunter, A

Genetic models of bone disease using ENU mutagenesis by Brown, S, Esapa, C, Barbaric, I, Hough, T, Brown, M, Croucher, P, Head, R, Chan, C, Crane, E, Cox, R, Cheeseman, M, Thakker, R

IDENTIFICATION OF NOVEL MOUSE MODELS OF CARDIOVASCULAR DEVELOPMENTAL MALFORMATIONS USING ETHYLNITROSOUREA MUTAGENESIS by Szumska, D, Pieles, G, Franklyn, A, Schneider, J, Clarke, K, Neubauer, S, Brown, S, Bhattacharya, S

Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a novel rapid mapping strategy. by Isaacs, A, Davies, K, Hunter, A, Nolan, P, Vizor, L, Peters, J, Gale, D, Kelsell, D, Latham, I, Chase, J, Fisher, E, Bouzyk, M, Potter, A, Masih, M, Walsh, F, Sims, M, Doncaster, K, Parsons, C, Martin, J, Brown, S, Rastan, S, Spurr, N, Gray, I

“…In order to address this phenotype gap, we have embarked on a genome-wide, phenotype-driven, large-scale N-ethyl-N--nitrosourea (ENU) mutagenesis screen for dominant mutations of clinical and pharmacological interest in the mouse. …”

A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse. by Isaacs, A, Oliver, P, Jones, E, Jeans, A, Potter, A, Hovik, B, Nolan, P, Vizor, L, Glenister, P, Simon, A, Gray, I, Spurr, N, Brown, S, Hunter, A, Davies, K

“…The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. …”

A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse by Isaacs, A, Oliver, P, Jones, E, Jeans, A, Potter, A, Hovik, B, Nolan, P, Vizor, L, Glenister, P, Simon, A, Gray, I, Spurr, N, Brown, S, Hunter, A, Davies, K

“…The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. …”

Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. by Keays, D, Tian, G, Poirier, K, Huang, G, Siebold, C, Cleak, J, Oliver, P, Fray, M, Harvey, R, Molnár, Z, Piñon, M, Dear, N, Valdar, W, Brown, S, Davies, K, Rawlins, J, Cowan, N, Nolan, P, Chelly, J, Flint, J

“…This study demonstrates the utility of ENU mutagenesis in the mouse as a means to discover the basis of human neurodevelopmental disorders.…”

Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. by Anstee, Q, Knapp, S, Maguire, E, Hosie, A, Thomas, P, Mortensen, M, Bhome, R, Martinez, A, Walker, SE, Dixon, C, Ruparelia, K, Montagnese, S, Kuo, Y, Herlihy, A, Bell, J, Robinson, I, Guerrini, I, McQuillin, A, Fisher, E, Ungless, M, Gurling, H, Morgan, M, Brown, S, Stephens, D, Belelli, D

“…Using N-ethyl-N-nitrosourea mutagenesis on an alcohol-averse background (F1 BALB/cAnN x C3H/HeH), we develop a mouse model exhibiting strong heritable preference for ethanol resulting from a dominant mutation (L285R) in Gabrb1. …”

Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations by Bull, K, Rimmer, A, Siggs, O, Miosge, L, Roots, C, Enders, A, Bertram, E, Crockford, T, Whittle, B, Potter, P, Simon, M, Mallon, A, Brown, S, Beutler, B, Goodnow, C, Lunter, G, Cornall, R

“…The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.…”

A requirement for Zic2 in the regulation of nodal expression underlies the establishment of left-sided identity by Dykes, I, Szumska, D, Kuncheria, L, Puliyadi, R, Chen, C, Papanayotou, C, Lockstone, H, Dubourg, C, David, V, Schneider, J, Keane, T, Adams, D, Brown, S, Mercier, S, Odent, S, Collignon, J, Bhattacharya, S

“…Analysis of ChiP-seq data, in vitro transcriptional assays and mutagenesis reveals a requirement for a low-affinity ZIC2 binding site for the activation of the Nodal enhancer HBE, which is normally active in node precursor cells. …”

microMRI-HREM pipeline for high-throughput, high-resolution phenotyping of murine embryos. by Pieles, G, Geyer, S, Szumska, D, Schneider, J, Neubauer, S, Clarke, K, Dorfmeister, K, Franklyn, A, Brown, S, Bhattacharya, S, Weninger, W

“…To demonstrate the potential of this methodology we show embryo phenotyping results produced in a large-scale ENU-mutagenesis study. In essence this represents an analysis pipeline, which starts with simultaneous micro-magentic resonance imaging (microMRI) screening (voxel size: 25.4 x 25.4 x 24.4 microm) of 32 embryos in one run. …”

A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways by Crompton, M, Purnell, T, Parker, A, Ball, G, Hardisty-Hughes, R, Gale, R, Williams, D, Dean, C, Simon, M, Mallon, A, Wells, S, Bhutta, M, Burton, M, Tateossian, H, Brown, S

“…Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM. …”

Analysis of the mouse mutant Cloth-ears shows a role for the voltage-gated sodium channel Scn8a in peripheral neural hearing loss. by Mackenzie, F, Parker, A, Parkinson, N, Oliver, P, Brooker, D, Underhill, P, Lukashkina, V, Lukashkin, A, Holmes, C, Brown, S

“…Using N-ethyl N-nitrosourea (ENU) mutagenesis to generate new mouse models of deafness, we identified a novel semi-dominant mouse mutant, Cloth-ears (Clth). …”

Autosomal dominant hypercalciuria in a mouse model due to a mutation of the epithelial calcium channel, TRPV5. by Loh, N, Bentley, L, Dimke, H, Verkaart, S, Tammaro, P, Gorvin, C, Stechman, M, Ahmad, B, Hannan, F, Piret, S, Evans, H, Bellantuono, I, Hough, T, Fraser, W, Hoenderop, J, Ashcroft, F, Brown, S, Bindels, R, Cox, R, Thakker, R

“…Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1). …”

edison - a novel model of otitis media by Crompton, M

“…A new mouse model of chronic OM, <em>edison</em>, was generated by <em>N</em>-ethyl-<em>N</em>-nitrosourea (ENU) mutagenesis and discovered in a recessive screen at MRC Harwell.…”