Nhlrc1-flox Mouse

Nhlrc1, which encodes an ubiquitin ligase, is associated with Lafora disease. It interacts with laforin encoded by EPM2A, and together they are thought to regulate critical neuronal functions [6]. Mutations in Nhlrc1 can lead to abnormal accumulation of polyglucosan bodies within neurons, resulting in progressive neurological signs, mainly myoclonic epilepsy [1,4,5,6,7].

In humans, the rare rs769301934 (NM_198586.3(NHLRC1): c.436 G > A; p.(Asp146Asn)) allele in Nhlrc1 is a common cause of Lafora disease in Turkey, and patients with Nhlrc1 mutations have a slower rate of disease progression compared to those with EPM2A mutations [5,7]. In dogs, a dodecamer expansion in Nhlrc1 has been identified in multiple breeds such as miniature wire-haired Dachshunds, Basset Hound, Beagle, Chihuahua, Pembroke Welsh Corgi, and Newfoundland dog, all diagnosed with Lafora disease [1,2,3,4].

In conclusion, Nhlrc1 is crucial in maintaining normal neuronal functions. Genetic studies in both humans and dogs with Lafora disease, which can be seen as in vivo research models, have revealed its role in this progressive neurological disorder. Understanding Nhlrc1's function provides insights into the mechanisms of Lafora disease, potentially guiding future treatment strategies.