Trapping genes expressed in the developing mouse inner ear

Wei, Yang; Musci, Teresa S.; Mansour, Suzanne L.

doi:10.1016/s0378-5955(97)00146-9

Cited by 9 publications

(18 citation statements)

References 38 publications

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“…A mouse ES cell line, designated 24-B9, was isolated from an ongoing gene trap screen that has been described previously (44). ␤-Gal activity was detected in undifferentiated 24-B9 cells and was insensitive to the application of a variety of different growth factors and hormones.…”

Section: Resultsmentioning

confidence: 99%

“…1A). The trapped sequences were not in frame with respect to the lacZ gene, suggesting that translation of the hybrid lacZ mRNA was initiated from the Kozak consensus ATG that is present on the gene trap vector (44).…”

Section: Resultsmentioning

confidence: 99%

“…X-Gal staining of adult tissues was performed on two individuals of each genotype for each punc strain. To examine expression patterns in more detail, embroys, brain slices, and inner ears were postfixed, dehydrated, embedded in paraffin, sectioned at 10 m, and counterstained with eosin as described previously (44).…”

mentioning

confidence: 99%

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Impaired Motor Coordination in Mice That Lackpunc

Wei

Mansour

2001

Molecular and Cellular Biology

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The punc gene, encoding a member of the neural cell adhesion molecule family expressed in the developing central nervous system, limbs, and inner ear, was identified. To extend studies of the normal expression pattern of punc and to determine its function, a mouse strain bearing a lacZ/neo insertion in a 5 coding exon was created. The complex pattern of punc expression in embryos from embryonic day 9.5 (E9.5) to E11.5 was mimicked accurately by ␤-galactosidase (␤-Gal) activity. As development proceeded, the distribution of ␤-Gal activity was increasingly restricted, finally becoming confined to the brain and inner ear by E15.5. In the adult, ␤-Gal activity was detected in several regions of the inner ear and brain and was particularly strong in the cerebellar Bergmann glia. Genetic analysis of this null allele demonstrated that punc is not required for normal embryogenesis. Interestingly, comparisons of ␤-Gal activity and punc transcripts in heterozygous and homozygous mutant individuals demonstrated that punc is negatively autoregulated in some tissues. Adult puncdeficient mice were overtly normal and had normal hearing. Compared with control littermates, however, homozygous mutants had significantly reduced retention times on the Rotarod, suggesting a role for Bergmann glia-expressed Punc in the cerebellar control of motor coordination.Neural cell adhesion molecules (NCAMs) play roles in both the developing and the adult central nervous system (CNS) NCAMs have a single-pass transmembrane domain or are anchored to the cell surface via a glycosylphosphatidyl inositol linkage. Their extracellular domains contain variable numbers of immunoglobulin (Ig) and fibronectin type III (FNIII) repeats, and their intracellular domains are noncatalytic, distinguishing them from the receptor protein tyrosine kinase and phosphatase subfamilies. NCAMs participate in homophilic and/or heterophilic binding interactions and, in some cases, soluble or matrix-bound ligands have been identified. Despite the fact that NCAMs do not have catalytic activity, they are thought to participate in signaling either by extracellular interactions with catalytic subfamily members or by intracellular interactions with signal adaptors (39, 41).NCAMs have complex, dynamic, and overlapping expression patterns during nervous system development. Many family members are also expressed widely in the adult. Thus, the expression and adhesive interaction data for a given family member can only provide clues to its function. Characterization of the phenotypes of mutants has been invaluable in determining the functions of these genes. To date, the phenotypes of individuals bearing mutations in the genes encoding four different NCAMs (NCAM, L1, DCC, and contactin) have been reported in vertebrates (1,5,6,9,10,15,17,27,37,38,45). Targeted ablation of these molecules substantiated other evidence that they function during development in axon guidance, fasciculation, and cell migration and linked specific developmental events to particular NCAMs. In contrast to th...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Impaired Motor Coordination in Mice That Lackpunc

Wei

Mansour

2001

Molecular and Cellular Biology

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“…3A). An nlsLacZSV40pA cassette was excised from a gene-trap vector (Yang et al, 1997), excluding the splice acceptor sequence, and inserted into the Dusp6 MscI site in exon 1, fusing the first 56 codons of the DUSP6 open reading frame (ORF) in-frame with the ␤gal ORF. A self-excising Neo r expression cassette (ACN) (Bunting et al, 1999) was placed immediately downstream of the LacZ gene for positive selection of targeted cell lines.…”

Section: Dusp6 Gene Targetingmentioning

confidence: 99%

Dusp6(Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development

et al. 2007

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Mitogen-activated protein kinase (MAPK) pathways are major mediators of extracellular signals that are transduced to the nucleus. MAPK signaling is attenuated at several levels, and one class of dual-specificity phosphatases, the MAPK phosphatases (MKPs), inhibit MAPK signaling by dephosphorylating activated MAPKs. Several of the MKPs are themselves induced by the signaling pathways they regulate, forming negative feedback loops that attenuate the signals. We show here that in mouse embryos, Fibroblast growth factor receptors (FGFRs) are required for transcription of Dusp6, which encodes MKP3, an extracellular signalregulated kinase (ERK)-specific MKP. Targeted inactivation of Dusp6 increases levels of phosphorylated ERK, as well as the pERK target, Erm, and transcripts initiated from the Dusp6 promoter itself. Finally, the Dusp6 mutant allele causes variably penetrant, dominant postnatal lethality, skeletal dwarfism, coronal craniosynostosis and hearing loss; phenotypes that are also characteristic of mutations that activate FGFRs inappropriately. Taken together, these results show that DUSP6 serves in vivo as a negative feedback regulator of FGFR signaling and suggest that mutations in DUSP6 or related genes are candidates for causing or modifying unexplained cases of FGFR-like syndromes.

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“…Another approach has been to pre-screen gene trap cell lines for lacZ expression that is regulated by differentiation and/or by the application of exogenous factors (Forrester et al, 1996;Baker et al, 1997;Bonaldo et al, 1998;Gajovic et al, 1998). We also described an induction gene trap screen aimed at enriching for trapped genes that are expressed in the developing mouse inner ear (Yang et al, 1997). In this report, we show that one of the genes identified in that screen is a novel mouse gene, which we named prtb (proline codon-rich transcript, brain expressed).…”

Section: Introductionmentioning

confidence: 99%