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Article ; Online: Evaluating neural crest cell migration in a Col4a1 mutant mouse model of ocular anterior segment dysgenesis.

Cozzitorto, Corinna / Peltz, Zoe / Flores, Lourdes M / Della Santina, Luca / Mao, Mao / Gould, Douglas B

Cells & development

2024 , Page(s) 203926

Abstract: The periocular mesenchyme (POM) is a transient migratory embryonic tissue derived from neural crest cells (NCCs) and paraxial mesoderm that gives rise to most of the structures in front of the eye. Morphogenetic defects of these structures can impair ... ...

Abstract	The periocular mesenchyme (POM) is a transient migratory embryonic tissue derived from neural crest cells (NCCs) and paraxial mesoderm that gives rise to most of the structures in front of the eye. Morphogenetic defects of these structures can impair aqueous humor outflow, leading to elevated intraocular pressure and glaucoma. Mutations in collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause Gould syndrome - a multisystem disorder often characterized by variable cerebrovascular, ocular, renal, and neuromuscular manifestations. Approximately one-third of individuals with COL4A1 and COL4A2 mutations have ocular anterior segment dysgenesis (ASD), including congenital glaucoma resulting from abnormalities of POM-derived structures. POM differentiation has been a major focus of ASD research, but the underlying cellular mechanisms are still unclear. Moreover, earlier events including NCC migration and survival defects have been implicated in ASD; however, their roles are not as well understood. Vascular defects are among the most common consequences of COL4A1 and COL4A2 mutations and can influence NCC survival and migration. We therefore hypothesized that NCC migration might be impaired by COL4A1 and COL4A2 mutations. In this study, we used 3D confocal microscopy, gross morphology, and quantitative analyses to test NCC migration in Col4a1 mutant mice. We show that homozygous Col4a1 mutant embryos have severe embryonic growth retardation and lethality, and we identified a potential maternal effect on embryo development. Cerebrovascular defects in heterozygous Col4a1 mutant embryos were present as early as E9.0, showing abnormal cerebral vasculature plexus remodeling compared to controls. We detected abnormal NCC migration within the diencephalic stream and the POM in heterozygous Col4a1 mutants whereby mutant NCCs formed smaller diencephalic migratory streams and POMs. In these settings, migratory NCCs within the diencephalic stream and POM localize farther away from the developing vasculature. Our results show for the first time that Col4a1 mutations lead to cranial NCCs migratory defects in the context of early onset defective angiogenesis without affecting cell numbers, possibly impacting the relation between NCCs and the blood vessels during ASD development.
Language	English
Publishing date	2024-05-09
Publishing country	Netherlands
Document type	Journal Article
ISSN	2667-2901
ISSN (online)	2667-2901
DOI	10.1016/j.cdev.2024.203926
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Article ; Online: Local Net Charge State of Collagen Triple Helix Is a Determinant of FKBP22 Binding to Collagen III.

Ishikawa, Yoshihiro / Bonna, Arkadiusz / Gould, Douglas B / Farndale, Richard W

International journal of molecular sciences

2023 Volume 24, Issue 20

Abstract: Mutations in ... ...

Abstract	Mutations in the
MeSH term(s)	Humans ; Tacrolimus Binding Proteins/metabolism ; Collagen/genetics ; Peptidylprolyl Isomerase/genetics ; Mutation ; Ehlers-Danlos Syndrome/genetics
Chemical Substances	FKBP22 (EC 5.2.1.-) ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; Collagen (9007-34-5) ; Peptidylprolyl Isomerase (EC 5.2.1.8) ; FKBP14 protein, human (EC 5.2.1.8)
Language	English
Publishing date	2023-10-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242015156
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Article ; Online: TGFβ Signaling Dysregulation May Contribute to COL4A1-Related Glaucomatous Optic Nerve Damage.

Mao, Mao / Kuo, Yien-Ming / Yu, Alfred K / Labelle-Dumais, Cassandre / Ou, Yvonne / Gould, Douglas B

Investigative ophthalmology & visual science

2024 Volume 65, Issue 5, Page(s) 15

Abstract: Purpose: Mutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta ( ... ...

Abstract	Purpose: Mutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFβ) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFβ signaling ameliorated ASD, supporting a role for the TGFβ pathway in disease pathogenesis. Here, we tested whether altered TGFβ signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice. Methods: To test the role of TGFβ signaling in glaucoma-relevant phenotypes, we genetically reduced TGFβ signaling using mice with mutated Tgfbr2, which encodes the common receptor for all TGFβ ligands in Col4a1+/G1344D mice. We performed slit-lamp biomicroscopy and optical coherence tomography for qualitative and quantitative analyses of anterior and posterior ocular segments, histological analyses of ocular tissues and optic nerves, and intraocular pressure assessments using rebound tonometry. Results: Col4a1+/G1344D mice showed defects of the ocular drainage structures, including iridocorneal adhesions, and phenotypes consistent with glaucomatous neurodegeneration, including thinning of the nerve fiber layer, retinal ganglion cell loss, optic nerve head excavation, and optic nerve degeneration. We found that reducing TGFβ receptor 2 (TGFBR2) was protective for ASD, ameliorated ocular drainage structure defects, and protected against glaucomatous neurodegeneration in Col4a1+/G1344D mice. Conclusions: Our results suggest that elevated TGFβ signaling contributes to glaucomatous neurodegeneration in Col4a1 mutant mice.
MeSH term(s)	Animals ; Mice ; Collagen Type IV/metabolism ; Collagen Type IV/genetics ; Signal Transduction/physiology ; Intraocular Pressure/physiology ; Glaucoma/metabolism ; Glaucoma/genetics ; Glaucoma/pathology ; Transforming Growth Factor beta/metabolism ; Tomography, Optical Coherence ; Receptor, Transforming Growth Factor-beta Type II/genetics ; Receptor, Transforming Growth Factor-beta Type II/metabolism ; Disease Models, Animal ; Optic Nerve Diseases/metabolism ; Optic Nerve Diseases/genetics ; Mice, Inbred C57BL ; Retinal Ganglion Cells/pathology ; Retinal Ganglion Cells/metabolism ; Anterior Eye Segment/metabolism ; Anterior Eye Segment/pathology ; Optic Nerve/pathology ; Optic Nerve/metabolism ; Slit Lamp Microscopy ; Phenotype ; Tonometry, Ocular ; Mutation
Chemical Substances	Collagen Type IV ; Transforming Growth Factor beta ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; Col4a1 protein, mouse ; Tgfbr2 protein, mouse (EC 2.7.11.30)
Language	English
Publishing date	2024-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.5.15
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Article ; Online: Elevated TGFβ signaling contributes to ocular anterior segment dysgenesis in Col4a1 mutant mice.

Mao, Mao / Labelle-Dumais, Cassandre / Tufa, Sara F / Keene, Douglas R / Gould, Douglas B

Matrix biology : journal of the International Society for Matrix Biology

2022 Volume 110, Page(s) 151–173

Abstract: Ocular anterior segment dysgenesis (ASD) refers to a collection of developmental disorders affecting the anterior structures of the eye. Although a number of genes have been implicated in the etiology of ASD, the underlying pathogenetic mechanisms remain ...

Abstract	Ocular anterior segment dysgenesis (ASD) refers to a collection of developmental disorders affecting the anterior structures of the eye. Although a number of genes have been implicated in the etiology of ASD, the underlying pathogenetic mechanisms remain unclear. Mutations in genes encoding collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause Gould syndrome, a multi-system disorder that often includes ocular manifestations such as ASD and glaucoma. COL4A1 and COL4A2 are abundant basement membrane proteins that provide structural support to tissues and modulate signaling through interactions with other extracellular matrix proteins, growth factors, and cell surface receptors. In this study, we used a combination of histological, molecular, genetic and pharmacological approaches to demonstrate that altered TGFβ signaling contributes to ASD in mouse models of Gould syndrome. We show that TGFβ signaling was elevated in anterior segments from Col4a1 mutant mice and that genetically reducing TGFβ signaling partially prevented ASD. Notably, we identified distinct roles for TGFβ1 and TGFβ2 in ocular defects observed in Col4a1 mutant mice. Importantly, we show that pharmacologically promoting type IV collagen secretion or reducing TGFβ signaling ameliorated ocular pathology in Col4a1 mutant mice. Overall, our findings demonstrate that altered TGFβ signaling contributes to COL4A1-related ocular dysgenesis and implicate this pathway as a potential therapeutic target for the treatment of Gould syndrome.
MeSH term(s)	Animals ; Basement Membrane/metabolism ; Collagen Type IV/genetics ; Collagen Type IV/metabolism ; Eye/metabolism ; Eye Abnormalities/metabolism ; Mice ; Mutation ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism
Chemical Substances	Col4a1 protein, mouse ; Collagen Type IV ; Transforming Growth Factor beta
Language	English
Publishing date	2022-05-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2022.05.001
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Article ; Online: Deletion of the Unfolded Protein Response Transducer IRE1α Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration.

Massoudi, Dawiyat / Gorman, Seán / Kuo, Yien-Ming / Iwawaki, Takao / Oakes, Scott A / Papa, Feroz R / Gould, Douglas B

Investigative ophthalmology & visual science

2023 Volume 64, Issue 4, Page(s) 30

Abstract: Purpose: The unfolded protein response (UPR) is triggered when the protein folding capacity of the endoplasmic reticulum (ER) is overwhelmed and misfolded proteins accumulate in the ER, a condition referred to as ER stress. IRE1α is an ER-resident ... ...

Abstract	Purpose: The unfolded protein response (UPR) is triggered when the protein folding capacity of the endoplasmic reticulum (ER) is overwhelmed and misfolded proteins accumulate in the ER, a condition referred to as ER stress. IRE1α is an ER-resident protein that plays major roles in orchestrating the UPR. Several lines of evidence implicate the UPR and its transducers in neurodegenerative diseases, including retinitis pigmentosa (RP), a group of inherited diseases that cause progressive dysfunction and loss of rod and cone photoreceptors. This study evaluated the contribution of IRE1α to photoreceptor development, homeostasis, and degeneration. Methods: We used a conditional gene targeting strategy to selectively inactivate Ire1α in mouse rod photoreceptors. We used a combination of optical coherence tomography (OCT) imaging, histology, and electroretinography (ERG) to assess longitudinally the effect of IRE1α deficiency in retinal development and function. Furthermore, we evaluated the IRE1α-deficient retina responses to tunicamycin-induced ER stress and in the context of RP caused by the rhodopsin mutation RhoP23H. Results: OCT imaging, histology, and ERG analyses did not reveal abnormalities in IRE1α-deficient retinas up to 3 months old. However, by 6 months of age, the Ire1α mutant animals showed reduced outer nuclear layer thickness and deficits in retinal function. Furthermore, conditional inactivation of Ire1α in rod photoreceptors accelerated retinal degeneration caused by the RhoP23H mutation. Conclusions: These data suggest that IRE1α is dispensable for photoreceptor development but important for photoreceptor homeostasis in aging retinas and for protecting against ER stress-mediated photoreceptor degeneration.
MeSH term(s)	Animals ; Mice ; Aging ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Retinal Degeneration/metabolism ; Retinitis Pigmentosa ; Rhodopsin/genetics ; Rhodopsin/metabolism ; Unfolded Protein Response ; Endoplasmic Reticulum Stress
Chemical Substances	Endoribonucleases (EC 3.1.-) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Rhodopsin (9009-81-8)
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.64.4.30
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Article ; Online: Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations.

Jeanne, Marion / Gould, Douglas B

Matrix biology : journal of the International Society for Matrix Biology

2017 Volume 57-58, Page(s) 29–44

Abstract: COL4A1 and COL4A2 are extracellular matrix proteins that form heterotrimers and are present in nearly all basement membranes in every organ. In the past decade, COL4A1 and COL4A2 mutations have been identified to cause a multi-system disorder for which ... ...

Abstract	COL4A1 and COL4A2 are extracellular matrix proteins that form heterotrimers and are present in nearly all basement membranes in every organ. In the past decade, COL4A1 and COL4A2 mutations have been identified to cause a multi-system disorder for which penetrance and severity of constituent phenotypes can greatly vary. Here, we compare the outcomes of more than 100 mutations identified in patients and data from a murine allelic series to explore the presence of genotype-phenotype correlations - many of which are shared among other types of collagen. We find that there is a frequency bias for COL4A1 over COL4A2 mutations and that glycine (Gly) substitutions within the triple helical domain are the most common class of mutations. Glycine is most often replaced by a charged amino acid, however the position of the mutation, and not the properties of the substituting amino acid, appears to have a greater influence on disease severity. Moreover, the impact of position is not straightforward. Observations from a murine allelic series suggest that mutations in the NC1 domain may result in relatively mild phenotypes via a 'quantitative' mechanism similar to other types of collagens, however, this effect was not apparent in human reports. Importantly, other position-dependent effects had differential impacts depending on the phenotype of interest. For example, the severity of cerebrovascular disease correlated with an amino-to-carboxy severity gradient for triple-helical glycine substitutions whereas the penetrance and severity of myopathy and nephropathy appear to involve a functional sub-domain(s). Greater understanding of genotype-phenotype correlations and the interaction of consequences of different mutations will be important for patient prognosis and care and for developing mechanism-based therapeutics to treat individual components of this emerging syndrome.
Language	English
Publishing date	2017-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2016.10.003
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Article ; Online: Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.

Yin, Mianmian / Smith, Jennifer A / Chou, Marissa / Chan, Jackie / Jittayasothorn, Yingyos / Gould, Douglas B / Caspi, Rachel R / Anderson, Mark S / DeFranco, Anthony L

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 5, Page(s) e2311487121

Abstract: Roughly one-half of mice with partial defects in two immune tolerance pathways ( ... ...

Abstract	Roughly one-half of mice with partial defects in two immune tolerance pathways (Aire
MeSH term(s)	Animals ; Mice ; Antigen Presentation ; Autoantigens ; Disease Models, Animal ; Mice, Inbred Strains ; Mice, Transgenic ; Receptors, Antigen, T-Cell
Chemical Substances	Autoantigens ; Receptors, Antigen, T-Cell ; Aire protein, mouse
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2311487121
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Article ; Online: Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome.

Mao, Mao / Popli, Tanav / Jeanne, Marion / Hoff, Kendall / Sen, Saunak / Gould, Douglas B

Disease models & mechanisms

2021 Volume 14, Issue 4

Abstract: Collagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that can affect any organ but typically involves the cerebral vasculature, eyes, ... ...

Abstract	Collagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that can affect any organ but typically involves the cerebral vasculature, eyes, kidneys and skeletal muscles. In recent years, patient advocacy and family support groups have united under the name of Gould syndrome. The manifestations of Gould syndrome are highly variable, and animal studies suggest that allelic heterogeneity and genetic context contribute to the clinical variability. We previously characterized a mouse model of Gould syndrome caused by a Col4a1 mutation in which the severities of ocular anterior segment dysgenesis (ASD), myopathy and intracerebral hemorrhage (ICH) were dependent on genetic background. Here, we performed a genetic modifier screen to provide insight into the mechanisms contributing to Gould syndrome pathogenesis and identified a single locus [modifier of Gould syndrome 1 (MoGS1)] on Chromosome 1 that suppressed ASD. A separate screen showed that the same locus ameliorated myopathy. Interestingly, MoGS1 had no effect on ICH, suggesting that this phenotype could be mechanistically distinct. We refined the MoGS1 locus to a 4.3 Mb interval containing 18 protein-coding genes, including Fn1, which encodes the extracellular matrix component fibronectin 1. Molecular analysis showed that the MoGS1 locus increased Fn1 expression, raising the possibility that suppression is achieved through a compensatory extracellular mechanism. Furthermore, we found evidence of increased integrin-linked kinase levels and focal adhesion kinase phosphorylation in Col4a1 mutant mice that is partially restored by the MoGS1 locus, implicating the involvement of integrin signaling. Taken together, our results suggest that tissue-specific mechanistic heterogeneity contributes to the variable expressivity of Gould syndrome and that perturbations in integrin signaling may play a role in ocular and muscular manifestations.
MeSH term(s)	Abnormalities, Multiple/genetics ; Animals ; Cerebral Hemorrhage/complications ; Chromosome Mapping ; Chromosomes, Mammalian/genetics ; Collagen Type IV/genetics ; Eye Abnormalities/complications ; Eye Abnormalities/genetics ; Fibronectins/genetics ; Fibronectins/metabolism ; Genes, Modifier ; Genes, Suppressor ; Genetic Loci ; Integrins/metabolism ; Mice, Mutant Strains ; Muscular Diseases/genetics ; Porencephaly/complications ; Signal Transduction ; Syndrome ; Mice
Chemical Substances	Col4a1 protein, mouse ; Collagen Type IV ; Fibronectins ; Integrins
Language	English
Publishing date	2021-04-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.048231
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Article ; Online: Use of sodium 4-phenylbutyrate to define therapeutic parameters for reducing intracerebral hemorrhage and myopathy in

Hayashi, Genki / Labelle-Dumais, Cassandre / Gould, Douglas B

Disease models & mechanisms

2018 Volume 11, Issue 7

Abstract: Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form heterotrimers that constitute a major component of nearly all basement membranes. ...

Abstract	Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form heterotrimers that constitute a major component of nearly all basement membranes.
MeSH term(s)	Aging/pathology ; Animals ; Animals, Newborn ; Cerebral Hemorrhage/complications ; Cerebral Hemorrhage/drug therapy ; Cerebral Hemorrhage/genetics ; Cerebral Hemorrhage/pathology ; Collagen Type IV/genetics ; Female ; Male ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Muscular Diseases/drug therapy ; Muscular Diseases/genetics ; Muscular Diseases/pathology ; Neuroprotective Agents/administration & dosage ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Phenylbutyrates/administration & dosage ; Phenylbutyrates/pharmacology ; Phenylbutyrates/therapeutic use ; Physical Conditioning, Animal ; Severity of Illness Index ; Time Factors
Chemical Substances	Col4a1 protein, mouse ; Collagen Type IV ; Neuroprotective Agents ; Phenylbutyrates ; 4-phenylbutyric acid (7WY7YBI87E)
Language	English
Publishing date	2018-07-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1754-8411
ISSN (online)	1754-8411
DOI	10.1242/dmm.034157
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Article ; Online: Lysyl hydroxylase 3-mediated post-translational modifications are required for proper biosynthesis of collagen α1α1α2(IV).

Ishikawa, Yoshihiro / Taga, Yuki / Coste, Thibault / Tufa, Sara F / Keene, Douglas R / Mizuno, Kazunori / Tournier-Lasserve, Elisabeth / Gould, Douglas B

The Journal of biological chemistry

2022 Volume 298, Issue 12, Page(s) 102713

Abstract: Collagens are the most abundant proteins in the body and among the most biosynthetically complex. A molecular ensemble of over 20 endoplasmic reticulum resident proteins participates in collagen biosynthesis and contributes to heterogeneous post- ... ...

Abstract	Collagens are the most abundant proteins in the body and among the most biosynthetically complex. A molecular ensemble of over 20 endoplasmic reticulum resident proteins participates in collagen biosynthesis and contributes to heterogeneous post-translational modifications. Pathogenic variants in genes encoding collagens cause connective tissue disorders, including osteogenesis imperfecta, Ehlers-Danlos syndrome, and Gould syndrome (caused by mutations in COL4A1 and COL4A2), and pathogenic variants in genes encoding proteins required for collagen biosynthesis can cause similar but overlapping clinical phenotypes. Notably, pathogenic variants in lysyl hydroxylase 3 (LH3) cause a multisystem connective tissue disorder that exhibits pathophysiological features of collagen-related disorders. LH3 is a multifunctional collagen-modifying enzyme; however, its precise role(s) and substrate specificity during collagen biosynthesis has not been defined. To address this critical gap in knowledge, we generated LH3 KO cells and performed detailed quantitative and molecular analyses of collagen substrates. We found that LH3 deficiency severely impaired secretion of collagen α1α1α2(IV) but not collagens α1α1α2(I) or α1α1α1(III). Amino acid analysis revealed that LH3 is a selective LH for collagen α1α1α2(IV) but a general glucosyltransferase for collagens α1α1α2(IV), α1α1α2(I), and α1α1α1(III). Importantly, we identified rare variants that are predicted to be pathogenic in the gene encoding LH3 in two of 113 fetuses with intracranial hemorrhage-a cardinal feature of Gould syndrome. Collectively, our findings highlight a critical role of LH3 in α1α1α2(IV) biosynthesis and suggest that LH3 pathogenic variants might contribute to Gould syndrome.
MeSH term(s)	Humans ; Collagen/metabolism ; Connective Tissue Diseases ; Glycosylation ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism ; Protein Processing, Post-Translational
Chemical Substances	Collagen (9007-34-5) ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase (EC 1.14.11.4)
Language	English
Publishing date	2022-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2022.102713
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