Through the human infantile stage, the progressive acquisition of the orthograde posture and bipedal locomotion is responsible for important morphostructural bony changes at the pelvis and the coxofemoral joint.
Among rotaviruses are the agents of human infantile diarrhea, Nebraska calf diarrhea, and epizootic diarrhea in infant mice [ 5].
To elucidate the molecular pathogenesis of TK2 deficiency, we generated a homozygous Tk2 H126N knock-in mutant (Tk2 −/− ) mouse that manifests a phenotype strikingly similar to the human infantile encephalomyopathy (Akman et al, 2008).
We generated and characterized thymidine kinase 2 H126N knock-in mouse model that recapitulates the human infantile encephalomyopathy and further demonstrated that the pathogenesis of the disorder is due to loss of Tk2 enzyme activity and unbalanced deoxynucleotide triphosphate (dNTP) pools with lack of deoxythymidine and deoxycytidine triphosphates.
Specifically, chondroitin sulfate proteoglycan 4, a cell surface proteoglycan is known to regulated in the adhesion, migration and invasion of tumor cells such as human melanoma and infantile acute myeloid leukemia [106].
Recently, loss-of-function mutations in the CYP24A1 gene have been found in some patients suffering from the rare human disease idiopathic infantile hypercalcaemia (IIH) [ 6].
In this work, we provide proof-of-concept of efficacy, tolerability and clinical relevance of combining CNS-directed approaches (transplant of gene-corrected NSCs or LV-based IC GT) with BMT to correct the GLD phenotype in a mouse model that recapitulates the severity and rapid progression of the early infantile human disease.
In humans, endemic Tyrolean infantile cirrhosis is genetically distinct from Wilson disease [ 25] and Bedlington terrier copper toxicosis [ 26].
Wolcott-Rallison syndrome was first reported in the early 1970s as a human disease characterized by infantile diabetes, multiple epiphyseal dysplasia and growth retardation [63], [64].
Common variations of each virus name were used in each database, specifically "astrovirus", "calicivirus", "norovirus", "Noro virus", "Norwalk", "Norwalk-like", "NLV", "NLVs", "SRSV", "winter vomiting disease", "Hyperemesis hiemis", "Snow Mountain", "sapovirus", "Sapporo virus", "Sapporo-like virus", "rotavirus", "duovirus", "human reovirus-like agent", and "infantile gastroenteritis agent".
As reported in this study and by our group previously, the majority of infantile cases the mutant human DAT retain 0 5% residual DAT activity whereas the human DAT mutants Ala314Val (atypical juvenile DTDS cases) retain higher residual dopamine.
