Glutaric aciduria type I (GA-I) is a rare organic aciduria caused by the autosomal recessive inherited deficiency of glutaryl-CoA dehydrogenase (GCDH).
Understanding how loss of LAMP-2 expression leads to cardiomyocyte dysfunction and heart failure has important implications for the treatment of Danon disease as well as a variety of other cardiac disorders associated with impaired autophagy.
Individuals with Hajdu-Cheney syndrome (HCS) present with osteoporosis, and HCS is associated with <i>NOTCH2</i> mutations causing deletions of the proline-, glutamic acid-, serine-, and threonine-rich (PEST) domain that are predicted to enhance NOTCH2 stability and cause gain-of-function.
We find that recombination of Plp1 in excitatory projection neurons does not cause neuropathology, whereas oligodendroglial targeting of Plp1 is sufficient to cause the entire neurodegenerative spectrum of SPG2 including axonopathy and secondary neuroinflammation.
SLC19A3 deficiency, also called thiamine metabolism dysfunction syndrome-2 (THMD2; OMIM 607483), is an autosomal recessive neurodegenerative disorder caused by mutations in SLC19A3, the gene encoding thiamine transporter 2.
Deletions and point mutations in SHANK3 cause Phelan-McDermid Syndrome (PMS), and have also been implicated in autism spectrum disorder (ASD) and intellectual disabilities, leading to the hypothesis that reduced SHANK3 expression impairs basic brain functions that are important for social communication and cognition.
New murine Niemann-Pick type C models bearing a pseudoexon-generating mutation recapitulate the main neurobehavioural and molecular features of the disease.
The X-linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology.
We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice.
Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.
The Fah(-/-) rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure, and renal tubular damage.
Mice homozygous for the Nbeal2 8 bp deletion (Nbeal2gps/gps) exhibit a phenotype similar to human GPS, with significantly reduced platelet counts compared to littermate controls (p = 1.63 x 10-7).
We created a mouse model reproducing the Hajdu Cheney syndrome by introducing a 6955C→T mutation in the Notch2 locus leading to a Q2319X change at the amino acid level.