Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2

IUBMB Life ◽  
2021 ◽  
Author(s):  
Lara Console ◽  
Maria Tolomeo ◽  
Jessica Cosco ◽  
Keith Massey ◽  
Maria Barile ◽  
...  
Keyword(s):  
Transporter Deficiency

scholarly journals The Role of Preclinical Models in Creatine Transporter Deficiency: Neurobiological Mechanisms, Biomarkers and Therapeutic Development

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1123
Author(s):  
Elsa Ghirardini ◽  
Francesco Calugi ◽  
Giulia Sagona ◽  
Federica Di Vetta ◽  
Martina Palma ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Human Condition ◽  
Clinical Aspects ◽  
Missense Mutations ◽  
Preclinical Development ◽  
Creatine Transporter Deficiency ◽  
Therapeutic Development ◽  
Transporter Deficiency ◽  
Scientific Challenge ◽  
Slc6a8 Gene

Creatine (Cr) Transporter Deficiency (CTD) is an X-linked metabolic disorder, mostly caused by missense mutations in the SLC6A8 gene and presenting with intellectual disability, autistic behavior, and epilepsy. There is no effective treatment for CTD and patients need lifelong assistance. Thus, the research of novel intervention strategies is a major scientific challenge. Animal models are an excellent tool to dissect the disease pathogenetic mechanisms and drive the preclinical development of therapeutics. This review illustrates the current knowledge about Cr metabolism and CTD clinical aspects, with a focus on mainstay diagnostic and therapeutic options. Then, we discuss the rodent models of CTD characterized in the last decade, comparing the phenotypes expressed within clinically relevant domains and the timeline of symptom development. This analysis highlights that animals with the ubiquitous deletion/mutation of SLC6A8 genes well recapitulate the early onset and the complex pathological phenotype of the human condition. Thus, they should represent the preferred model for preclinical efficacy studies. On the other hand, brain- and cell-specific conditional mutants are ideal for understanding the basis of CTD at a cellular and molecular level. Finally, we explain how CTD models might provide novel insight about the pathogenesis of other disorders, including cancer.

Erythroid urea transporter deficiency due to novel JKnullalleles

Transfusion ◽  
2007 ◽  
Vol 0 (0) ◽  
pp. 071121030748009-??? ◽  
Author(s):  
Elisabet S. Wester ◽  
Susan T. Johnson ◽  
Tama Copeland ◽  
Ranjan Malde ◽  
Edmond Lee ◽  
...  
Keyword(s):  
Urea Transporter ◽  
Transporter Deficiency

The clinical syndrome of creatine transporter deficiency

2003 ◽  
pp. 45-48 ◽  
Author(s):  
Ton J. deGrauw ◽  
Kim M. Cecil ◽  
Anna W. Byars ◽  
Gajja S. Salomons ◽  
William S. Ball ◽  
...  
Keyword(s):  
Clinical Syndrome ◽  
Creatine Transporter ◽  
Creatine Transporter Deficiency ◽  
Transporter Deficiency

scholarly journals A novel mouse model of creatine transporter deficiency

F1000Research ◽  
2015 ◽  
Vol 3 ◽  
pp. 228
Author(s):  
Laura Baroncelli ◽  
Maria Grazia Alessandrì ◽  
Jonida Tola ◽  
Elena Putignano ◽  
Martina Migliore ◽  
...  
Keyword(s):  
Mouse Model ◽  
Murine Model ◽  
Deficiency Syndrome ◽  
Speech Impairment ◽  
Behavioral Disturbances ◽  
Creatine Transporter ◽  
Creatine Transporter Deficiency ◽  
Creatine Deficiency ◽  
Creatine Deficiency Syndrome ◽  
Transporter Deficiency

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement  and behavioral disturbances, language and speech impairment ( OMIM #300352).CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/y murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.

scholarly journals ABCA2 transporter deficiency reduces incidence of TRAMP prostate tumor metastasis and cellular chemotactic migration

2011 ◽  
Vol 300 (2) ◽  
pp. 154-161 ◽  
Author(s):  
Jody T. Mack ◽  
Kristi L. Helke ◽  
Gabrielle Normand ◽  
CoDanielle Green ◽  
Danyelle M. Townsend ◽  
...  
Keyword(s):  
Tumor Metastasis ◽  
Prostate Tumor ◽  
Chemotactic Migration ◽  
Transporter Deficiency
Sign in / Sign up

Export Citation Format

Share Document