Delayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance.
Slc7a7
Arginine
IGF-1
Lysinuric protein intolerance
Osteoblast
Osteoporosis
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
received:
07
02
2023
accepted:
14
07
2023
medline:
18
8
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
ppublish
Résumé
SLC7A7 deficiency, or lysinuric protein intolerance (LPI), causes loss of function of the y+LAT1 transporter critical for efflux of arginine, lysine and ornithine in certain cells. LPI is characterized by urea cycle dysfunction, renal disease, immune dysregulation, growth failure, delayed bone age and osteoporosis. We previously reported that Slc7a7 knockout mice (C57BL/6×129/SvEv F2) recapitulate LPI phenotypes, including growth failure. Our main objective in this study was to characterize the skeletal phenotype in these mice. Compared to wild-type littermates, juvenile Slc7a7 knockout mice demonstrated 70% lower body weights, 87% lower plasma IGF-1 concentrations and delayed skeletal development. Because poor survival prevents evaluation of mature knockout mice, we generated a conditional Slc7a7 deletion in mature osteoblasts or mesenchymal cells of the osteo-chondroprogenitor lineage, but no differences in bone architecture were observed. Overall, global Slc7a7 deficiency caused growth failure with low plasma IGF-1 concentrations and delayed skeletal development, but Slc7a7 deficiency in the osteoblastic lineage was not a major contributor to these phenotypes. Future studies utilizing additional tissue-specific Slc7a7 knockout models may help dissect cell-autonomous and non-cell-autonomous mechanisms underlying phenotypes in LPI.
Identifiants
pubmed: 37486182
pii: 324835
doi: 10.1242/dmm.050118
pmc: PMC10445726
pii:
doi:
Substances chimiques
Amino Acid Transport System y+L
0
Insulin-Like Growth Factor I
67763-96-6
Slc7a7 protein, mouse
0
insulin-like growth factor-1, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK106453
Pays : United States
Organisme : NIH HHS
ID : S10 OD016167
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM139534
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007526
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD061221
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NIH HHS
ID : U54HD061221
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007664
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32GM07526
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006348
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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