WFDC2 gene deletion in mouse led to severe dyspnea and type-I alveolar cell apoptosis

Zhang, Taojun; Long, Haiyan; Li, Jinping; Chen, Zhenwen; Wang, Fengchao; Jiang, Shi‐Wen

doi:10.1016/j.bbrc.2019.11.011

Cited by 13 publications

(14 citation statements)

References 26 publications

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“…Our automated analysis of E14.5 Wfdc2 -/embryos revealed two significantly smaller organ volumes: those of the trachea and bronchi, which are novel findings for this gene. These overlap broadly with the locations of the previously reported pulmonaryspecific abnormalities in Wfdc2 -/mice, including the absence of mature club cells from the bronchi and trachea, postnatally-collapsed lung, reduced lung surfactant levels (Nakajima et al, 2019), and alveoli abnormalities (Zhang et al, 2020). The novel phenotypes reported here bring forward the time when gross abnormalities due to loss of Wfdc2 first become visible during embryo development (previously postnatally), and therefore add new temporal information to the role of Wfdc2 in pulmonary development.…”

Section: Development • Accepted Manuscriptsupporting

confidence: 85%

LAMA: automated image analysis for the developmental phenotyping of mouse embryos

et al. 2021

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Advanced 3D imaging modalities, such as micro computed tomography (micro-CT), have been incorporated into the high-throughput embryo pipeline of the International Mouse Phenotyping Consortium (IMPC). This project generates large volumes of raw data that cannot be immediately exploited without significant resources of manpower and expertise. Thus, rapid automated annotation is critical to ensure that 3D imaging data can be integrated with other multi-dimensional phenotyping data. We present an automated computational mouse embryo phenotyping pipeline, which harnesses the large amount of wild type control data available in the IMPC embryo pipeline in order to address issues of low mutant sample number as well as incomplete penetrance and variable expressivity. We also investigate the effect of developmental substage on automated phenotyping results. Designed primarily for developmental biologists, our software performs image pre-processing, registration, statistical analysis and segmentation of embryo images. We also present a novel anatomical E14.5 embryo atlas average and using it with LAMA show that we can uncover known and novel dysmorphology from two IMPC knockout lines.

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Section: Development • Accepted Manuscriptsupporting

confidence: 85%

LAMA: automated image analysis for the developmental phenotyping of mouse embryos

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…Recently, independent Wfdc2 deficient mouse lines have been generated and shown to have an embryonic lethal phenotype [23,24]. Wfdc2 -/mice die at, or soon after, birth from respiratory failure [23,24]. Wfdc2 -/newborn mice exhibit atelectasis and unsurprisingly exhibit a significant enhanced inflammatory profile, that is lacking from lungs preterm [23].…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies against murine Wfdc2 were generated using three distinct polypeptides covering different regions of the protein: Ac-CPISATGTDAEKPGE-amide (amino acids [22][23][24][25][26][27][28][29][30][31][32][33][34][35]; Ac-CPNGPSEGELSGTDTKLSE-amide (amino acids 73-90); Ac-KPPAVTREGLGVREKQGTCamide (amino acids 114-132). The polypeptides were HPLC purified.…”

Section: Generation and Characterisation Of Mouse Specific Wfdc2 Antimentioning

confidence: 99%

“…Some evidence suggests that WFDC2 may be a marker of other diseases [20,21] and functions in innate defence of the gut [22]. Recently, two studies have unexpectedly shown that loss of WFDC2 leads to a respiratory insufficiency and embryonic lethality [23,24]. The driver of this phenotype remains unresolved.…”

Section: Introductionmentioning

confidence: 99%

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Expression and function of murine WFDC2 in the respiratory tract

Bingle

Armes

Williams

et al. 2020

Preprint

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WFDC2/HE4 encodes a poorly characterised secretory protein that shares structural similarity with multifunctional host defence proteins through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. WFDC2 is expressed in multiple epithelia and although its' function remains unresolved, it is also overexpressed in a number of human cancers and has an established role as a cancer marker. Currently, little is known about the distribution of WFDC2 in the mouse and thus we have systematically analysed the mouse wfdc2 gene, its' expression and distribution. We have used recombinant WFDC2 for functional studies. Wfdc2 is the most highly expressed family member in the lung and is enriched in the nasopharynx. Wfdc2 is the most highly expressed family member in differentiated epithelial cells isolated from the trachea, nasal passages and middle ear. Wfdc2 consists of 5 exons with exon 3 encoding an unstructured linker region that separates the two WFDC domains. This genomic organisation appears to be restricted to the Muridae and Cricetidae families of rodents.Similar to the situation in man, mouse wfdc2 can be alternatively spliced to yield a number of distinct transcripts that have the potential to generate a repertoire of distinct protein isoforms.We used immunohistochemistry to localise the proteins to tissues of the respiratory tract and head and neck regions. Although the protein was limited to epithelial cells of the respiratory tract and nasal and oral cavities, it was expressed in different cells in different regions suggesting expression is governed by a unique regulatory mechanism. Recombinant WFDC2 did not possess antiproteinase activity against trypsin or elastase and had no clear antimicrobial activity.

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HE4 overexpression in mice leads to leydig cell hyperplasia and spermatogensis impairment: Pathological implications for oligospermia

Ling

Tang

Lin

et al. 2023

Molecular and Cellular Endocrinology

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WFDC2 gene deletion in mouse led to severe dyspnea and type-I alveolar cell apoptosis

Cited by 13 publications

References 26 publications

LAMA: automated image analysis for the developmental phenotyping of mouse embryos

LAMA: automated image analysis for the developmental phenotyping of mouse embryos

Expression and function of murine WFDC2 in the respiratory tract

HE4 overexpression in mice leads to leydig cell hyperplasia and spermatogensis impairment: Pathological implications for oligospermia

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