Venditti, Charles (NHGRI)
Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by the deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). It is characterized by metabolic instability, multiorgan pathology, and poor prognosis for long-term survival. To study MMA caused by MUT deficiency, a series of murine models have been constructed using gene targeting and analyzed. The model is a full knock out of the mouse Mut gene that produces neonatal lethality on the C57Bl6/Sv129 background. Another embodiment of this allele is used to create a related mouse model of Mut deficiency that can survive the immediate neonatal period and therefore be used to study the effects of MMA on an older animal, which is larger and easier to manipulate. To derive this model, C57Bl6/Sv129 Mut +/- mice are crossed to FvBN mice to create (C57Bl6/Sv129) FvBN Mut +/- carriers, which are intercrossed to generate (C57Bl6/Sv129) FvBN Mut -/- in the G2. A subset of such full knock outs are viable and can be very useful for pathophysiology and to assess MUT therapeutics. This transgenic mouse model is a valuable research tool to further understand the pathological mechanism of MMA and can be used to develop and assess targeted treatments
This transgenic mouse model is a valuable research tool to further understand the pathological mechanism of MMA and can be used to develop and assess targeted treatments.
- Cells from these mice can be extracted and used to create in vitro and ex vivo models as well as stem cells
- This allele can be used to create new animal models, by combined it with germ line or viral transgenes, or small molecules