A hypomorphic allele reveals an important role of inturned in mouse skeletal development
Open accessAbstract
Background: Cilia are important for Hedgehog signaling in vertebrates and many genes that encode proteins involved in ciliogenesis have been studied for their roles in embryonic development. Null mutations in many of these genes cause early embryonic lethality, hence an understanding of their roles in postnatal development is limited. Results: The Inturned (Intu) gene is required for ciliogenesis and here we report a recessive hypomorphic mutation, resulting in substitution of a conserved hydrophobic residue (I813N) near the C‐terminus, that sheds light on later functions of Intu. Mice homozygous for this Double‐thumb (Intu Dtm) allele exhibit polydactyly, retarded growth, and reduced survival. There is a moderate loss of cilia in Intu Dtm/Dtm mutants, and Intu I813N exhibits compromised ability to increase ciliogenesis in cultured Intu null mutant cells. Intu Dtm mutants show rib defects and delay of endochondral ossification in long bones, digits, vertebrae, and the sternum. These skeletal defects correlate with a decrease in Hh signaling. However, patterning of the neural tube and planar cell polarity appear to be normal. Conclusions: This hypomorphic Intu allele highlights an important role of Intu in mouse skeletal development. Developmental Dynamics 244:736–747, 2015. © 2015 Wiley Periodicals, Inc.
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Heterozygous Intu mutant mice showed a significant trend of reduction in body length.
“Furthermore, the heterozygous Intu mutant mice showed a significant trend of reduction in body length and fore and hind limb length (S8 Fig), which was consistent with previous findings [13].”
From Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci (2023) · cites this paper as [13]
The Results section, ‘IntuDtm mutant mice exhibit growth retardation’ (page unavailable), says the mutants were significantly smaller than both wild-type and heterozygous littermates. The Introduction identifies the mice with stunted growth as homozygous mutants. The paper therefore attributes reduced growth to homozygous mice, not the heterozygous mice named in the claim; it does not report a significant reduction in heterozygous body length. (LLM, conf=0.85)
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Experimental — accuracy not yet measuredHeterozygous Intu mutant mice showed a significant trend of reduction in fore and hind limb length.
“Furthermore, the heterozygous Intu mutant mice showed a significant trend of reduction in body length and fore and hind limb length (S8 Fig), which was consistent with previous findings [13].”
From Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci (2023) · cites this paper as [13]
The Results section on growth retardation reports that homozygous IntuDtm mutants were smaller than their wild-type and heterozygous littermates. The Results section on forelimb bones reports delayed ossification in mutants, not reduced fore- and hindlimb length in heterozygotes. The paper supports a general link between Intu mutation and impaired skeletal growth, but not the specific heterozygote finding. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRecent studies have suggested an important role of Intu in mouse skeletal development.
“Recent studies have suggested an important role of Intu in mouse skeletal development [13].”
From Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci (2023) · cites this paper as [13]
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- Authors
- Chang, R., Petersen, J. R., Niswander, L. A., & Liu, A.
- Affiliations
- Pennsylvania State University (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Liu, Aimin
- Venue
- Developmental Dynamics
- Publisher
- Wiley
- Published
- 2015-05-25
- Volume
- 244
- Issue
- 6
- Pages
- 736-747
- ISSN
- 1058-8388 (ISSN-L)
- 1097-0177
- PMC
- PMC4449324
- OpenAlex
- W1767655607
- Cited by
- 18
- References
- 25
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 5
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Developmental Dynamics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- PKD Foundation (02YI08a)
- Pennsylvania State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Keywords
- ciliogenesis, hypomorphic allele, Hedgehog signaling, skeletal development, polydactyly, endochondral ossification, rib defects, postnatal development, mouse mutants, planar cell polarity
- MeSH terms
- Abnormalities, Multiple, Patched Receptors, Alleles, Amino Acid Sequence, Animals, Bone and Bones, Cells, Cultured, Cilia, Growth Disorders, Membrane Proteins, Molecular Sequence Data, Neural Tube Defects, Osteogenesis, Receptors, Cell Surface, Signal Transduction, Sequence Alignment, Cell Polarity, Point Mutation, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Polydactyly, Amino Acid Substitution, Mutation, Missense, Mice, Hedgehog Proteins
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