Generation and characterization of Lhx3GFP reporter knockin and Lhx3loxP conditional knockout mice

Xu, Mei; Xie, Xiaoling; Dong, Xuhui; Liang, Guozheng; Gan, Lin

doi:10.1002/dvg.23098

Cited by 4 publications

(4 citation statements)

References 20 publications

(24 reference statements)

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“…TFs are known drivers of tissue development and identity maintenance ( Uhlen et al, 2015 ). We observed high enrichment of the LHX family motif in the retina, which plays an important role in pituitary hormone deficiency associated with ocular defects ( Pérez et al, 2012 ; Xu et al, 2018 ). The second mechanism is the direct regulation of adjacent tissue-specific functional genes.…”

Section: Discussionmentioning

confidence: 88%

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

Zhu¹,

Wang²,

Li³

et al. 2023

Zoological Research

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The development of epigenetic maps, such as the ENCODE project in humans, provides resources for gene regulation studies and a reference for research of disease-related regulatory elements. However, epigenetic information, such as a bird-specific chromatin accessibility atlas, is currently lacking for the thousands of bird species currently described. The major genomic difference between birds and mammals is their shorter introns and intergenic distances, which seriously hinders the use of humans and mice as a reference for studying the function of important regulatory regions in birds. In this study, using chicken as a model bird species, we systematically compiled a chicken chromatin accessibility atlas using 53 Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) samples across 11 tissues. An average of 50 796 open chromatin regions were identified per sample, cumulatively accounting for 20.36% of the chicken genome. Tissue specificity was largely reflected by differences in intergenic and intronic peaks, with specific functional regulation achieved by two mechanisms: recruitment of several sequence-specific transcription factors and direct regulation of adjacent functional genes. By integrating data from genome-wide association studies, our results suggest that chicken body weight is driven by different regulatory variants active in growth-relevant tissues. We propose CAB39L (active in the duodenum), RCBTB1 (muscle and liver), and novel long non-coding RNA ENSGALG00000053256 (bone) as candidate genes regulating chicken body weight. Overall, this study demonstrates the value of epigenetic data in fine-mapping functional variants and provides a compendium of resources for further research on the epigenetics and evolution of birds and mammals.

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Section: Discussionmentioning

confidence: 88%

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

Zhu¹,

Wang²,

Li³

et al. 2023

Zoological Research

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“…First, we compared the expression of MYO6, LHX3, and SOX2 in developing inner ears of wild‐type control and homozygous Gfi1 GCE/GCE mice at E13.5‐E17.5. The expression of hair cell markers MYO6 and LHX3 started in vestibular hair cells at E13.5 and in cochlear hair cells at E15.5 (Xu, Xie, Dong, Liang, & Gan, ), and Gfi1 GCE/GCE mice had no detectable effect on the onset and maintenance of MYO6 and LHX3 expression in the hair cells (Figure a, b). Likewise, anti‐SOX2 immunolabeling showed that the homozygous GCE knock‐in did not affect SOX2 expression in the supporting cells (Figure c), indicating normal inner ear development in Gfi1 GCE/GCE homozygotes.…”

Section: Resultsmentioning

confidence: 99%

Gfi1‐GCE inducible Cre line for hair cell‐specific gene manipulation in mouse inner ear

Tang

et al. 2019

Genesis

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Tissue-specific inducible Cre recombinase mouse lines allow precise genetic manipulations in spatiotemporal manners and are pivotal for functional studies of genes during development and in adults. Growth factor independence 1 (GFI1) is an essential transcription factor expressed in the hair cells of mouse inner ear and Gfi1 locus serves as an excellent anchor site to drive the expression of inducible Cre recombinase in mouse inner hair cells. In this study, we have generated Gfi1-P2A-GFP-CreERT2 (Gfi1-GCE) knock-in mouse line by in-frame fusion of a selfcleaving GCE to the C-terminus of GFI1. We have shown that as predicted, the expression of GCE and GFI1 was detected specifically in the cytosol and nuclei of hair cells, respectively, of uninduced Gfi1-GCE mice, suggesting the successful cleavage and simultaneous expression of GFI1 and GCE. In addition, the in-frame fusion of the self-cleaving GCE does not interrupt the function of Gfi1 in the inner ear. Administration of tamoxifen leads to nuclear translocation of GCE and results in an efficient activation of tdTomato reporter gene expression specifically in most hair cells throughout development and in adults. Thus, this inducible Gfi1-GCE mouse line is a highly efficient Cre deleter and is suitable for gene manipulation in developing and adult inner ear hair cells.

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“…The function and regulation of LHX3 have been studied in mouse models. 6,20,21 LHX3 knockout mice were stillborn or died within 24 h of birth, likely because of nervous system deficits, and they lacked anterior and intermediate pituitary lobes, with 4 of the 5 hormone-secreting anterior cell types absent. 6 Reduced expression of both LHX3 messenger RNA and protein in the Rathke pouch, the location from which the anterior and intermediate lobes of the pituitary and thereby the sites of the various types of hormone-producing endocrine cells develop, resulted in severe hypoplasia of the pouch and increased apoptosis.…”

Section: Brief Reportmentioning

confidence: 99%

Dwarfism in Tibetan Terrier dogs with an LHX3 mutation

Thaiwong

Corner

Forge³

et al. 2021

J VET Diagn Invest

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Canine pituitary dwarfism in German Shepherd and related dog breeds has been reported to be associated with a 7-bp deletion mutation in intron 5 of the LHX3 gene. This mutation is transmitted as an autosomal recessive trait that results in dwarf dogs with significantly smaller stature and abnormal haircoat, and potentially early death. Phenotypically, affected adult dogs are proportionally dwarfs. These dwarfs also have a soft, woolly puppy coat that fails to transition into the typical adult hair coat, and marked hair loss occurs in some dogs. We report a similar manifestation of dwarfism in Tibetan Terriers with the same LHX3 mutation. Dwarf Tibetan Terrier puppies were born physically normal but failed to gain weight or to grow at the same rate as their normal littermates. The 7-bp deletion mutation of the LHX3 gene was identified in both alleles of 3 Tibetan Terrier dwarfs from 3 litters, which were biologically related. All parents of these dogs are carriers, confirming transmission of dwarfism in an autosomal recessive manner. Recognition and detection of this mutation will help in guiding future breeding plans to eventually eliminate this trait from Tibetan Terriers.

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Generation and characterization of Lhx3^GFP reporter knockin and Lhx3^loxP conditional knockout mice

Cited by 4 publications

References 20 publications

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

Gfi1‐GCE inducible Cre line for hair cell‐specific gene manipulation in mouse inner ear

Dwarfism in Tibetan Terrier dogs with an LHX3 mutation

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