Article Navigation
- < Previous
- Next >
Journal Article
Get access
, Tess Holling Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Laura Brylka Department of Osteology and Biomechanics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Tasja Scholz Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Tatjana Bierhals Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Theresia Herget Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Peter Meinecke Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Ralf Oheim Department of Osteology and Biomechanics University Medical Center Hamburg‐Eppendorf Hamburg Germany Search for other works by this author on: Oxford Academic Kerstin Kutsche Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany Address correspondence to: Kerstin Kutsche, PhD, Institute of Human Genetics, University Medical Center Hamburg‐Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. E‐mail: kkutsche@uke.de Search for other works by this author on: Oxford Academic
https://orcid.org/0000-0001-9449-5013 Journal of Bone and Mineral Research, Volume 38, Issue 9, 1 September 2023, Pages 1334–1349, https://doi.org/10.1002/jbmr.4827
Published:
01 September 2023
Article history
Received:
08 August 2022
Revision received:
27 April 2023
Accepted:
07 May 2023
Published:
01 September 2023
- Views
- Article contents
- Figures & tables
- Video
- Audio
- Supplementary Data
-
Cite
Cite
Tess Holling, Laura Brylka, Tasja Scholz, Tatjana Bierhals, Theresia Herget, Peter Meinecke, Thorsten Schinke, Ralf Oheim, Kerstin Kutsche, TMCO3, a Putative K+:Proton Antiporter at the Golgi Apparatus, Is Important for Longitudinal Growth in Mice and Humans, Journal of Bone and Mineral Research, Volume 38, Issue 9, 1 September 2023, Pages 1334–1349, https://doi.org/10.1002/jbmr.4827
Close
Search
Close
Search
Advanced Search
Search Menu
Abstract
Isolated short stature, defined as short stature without any other abnormalities, is a common heterogeneous condition in children. Exome sequencing identified the hom*ozygous nonsense variant c.1832G>A/p.(Trp611*) in TMCO3 in two sisters with isolated short stature. Radiological studies, biochemical measurements, assessment of the skeletal status, and three‐dimensional bone microarchitecture revealed no relevant skeletal and bone abnormalities in both sisters. The hom*ozygous TMCO3 variant segregated with short stature in the family. TMCO3 transcript levels were reduced by ~50% in leukocyte‐derived RNA of both sisters compared with controls, likely due to nonsense‐mediated mRNA decay. In primary urinary cells of heterozygous family members, we detected significantly reduced TMCO3 protein levels. TMCO3 is functionally uncharacterized. We ectopically expressed wild‐type TMCO3 in HeLa and ATDC5 chondrogenic cells and detected TMCO3 predominantly at the Golgi apparatus, whereas the TMCO3W611* mutant did not reach the Golgi. Coordinated co‐expression of TMCO3W611*‐HA and EGFP in HeLa cells confirmed intrinsic instability and/or degradation of the mutant. Tmco3 is expressed in all relevant mouse skeletal cell types. Highest abundance of Tmco3 was found in chondrocytes of the prehypertrophic zone in mouse and minipig growth plates where it co‐localizes with a Golgi marker. Knockdown of Tmco3 in differentiated ATDC5 cells caused reduced and increased expression of Pthlh and Ihh, respectively. Measurement of long bones in Tmco3tm1b(KOMP)Wtsi knockout mice revealed significant shortening of forelimbs and hindlimbs. TMCO3 is a potential member of the monovalent cation:proton antiporter 2 (CPA2) family. By in silico tools and hom*ology modeling, TMCO3 is predicted to have an N‐terminal secretory signal peptide, forms a dimer localized to the membrane, and is organized in a dimerization and a core domain. The core domain contains the CPA2 motif essential for K+ binding and selectivity. Collectively, our data demonstrate that loss of TMCO3 causes growth defects in both humans and mice. © 2023 American Society for Bone and Mineral Research (ASBMR).
AUTOSOMAL RECESSIVE, EXOME SEQUENCING, EXTRACELLULAR MATRIX, ION:PROTON ANTIPORTER, MONOGENIC
© 2023 American Society for Bone and Mineral Research
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Issue Section:
research articles
You do not currently have access to this article.
Download all slides
Sign in
Get help with access
-
American Society for Bone and Mineral Research members
Personal account
- Sign in with email/username & password
- Get email alerts
- Save searches
- Purchase content
- Activate your purchase/trial code
- Add your ORCID iD
Sign in Register
Institutional access
- Sign in with a library card
- Sign in with username/password
- Recommend to your librarian
Sign in through your institution
Sign in through your institution
Institutional account management
Sign in as administrator
Get help with access
Institutional access
Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:
IP based access
Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.
Sign in through your institution
Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution’s website and Oxford Academic.
- Click Sign in through your institution.
- Select your institution from the list provided, which will take you to your institution's website to sign in.
- When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If your institution is not listed or you cannot sign in to your institution’s website, please contact your librarian or administrator.
Sign in with a library card
Enter your library card number to sign in. If you cannot sign in, please contact your librarian.
Society Members
Society member access to a journal is achieved in one of the following ways:
Sign in through society site
Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:
- Click Sign in through society site.
- When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If you do not have a society account or have forgotten your username or password, please contact your society.
Sign in using a personal account
Some societies use Oxford Academic personal accounts to provide access to their members. See below.
Personal account
A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.
Some societies use Oxford Academic personal accounts to provide access to their members.
Viewing your signed in accounts
Click the account icon in the top right to:
- View your signed in personal account and access account management features.
- View the institutional accounts that are providing access.
Signed in but can't access content
Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.
Institutional account management
For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.
Purchase
Subscription prices and ordering for this journal
Purchasing options for books and journals across Oxford Academic
Short-term Access
To purchase short-term access, please sign in to your personal account above.
Don't already have a personal account? Register
TMCO3, a Putative K+:Proton Antiporter at the Golgi Apparatus, Is Important for Longitudinal Growth in Mice and Humans - 24 Hours access
EUR €46.00
GBP £40.00
USD $49.00
Rental
This article is also available for rental through DeepDyve.
Advertisem*nt
Citations
Views
128
Altmetric
More metrics information
Metrics
Total Views 128
101 Pageviews
27 PDF Downloads
Since 2/1/2024
| Month: | Total Views: |
|---|---|
| February 2024 | 15 |
| March 2024 | 42 |
| April 2024 | 39 |
| May 2024 | 32 |
Citations
Powered by Dimensions
Altmetrics
Email alerts
Article activity alert
Advance article alerts
New issue alert
Receive exclusive offers and updates from Oxford Academic
Email alerts
Advance article alerts
New issue alert
Receive exclusive offers and updates from Oxford Academic
Related articles in
- Google Scholar
Citing articles via
Google Scholar
-
Latest
-
Most Read
-
Most Cited
More from Oxford Academic
Clinical Medicine
Endocrinology and Diabetes
Medicine and Health
Books
Journals
Advertisem*nt
