Genetic basis of Brain hypomyelination in Weimaraners - is caused by a frameshift mutation in the FNIP2 gene (folliculin-interacting protein 2). This mutation is a deletion of a single nucleotide (c.880delA) in exon 9 of FNIP2, leading to a truncated protein and loss of function. The disease is inherited in an autosomal recessive pattern, meaning affected dogs have two copies of the mutated gene, while carriers have one copy and appear normal but can pass the mutation on. The mutation causes a disruption in the normal development and maturation of oligodendrocytes, the cells responsible for forming myelin in the central nervous system (CNS). The gene is located on canine chromosome 15.
Pathophysiology - Oligodendrocytes fail to mature properly, leading to reduced production or absence of myelin in the brain and spinal cord axons. Hypomyelination affects primarily the peripheral areas of the ventral and lateral funiculi of the spinal cord, with a notable deficit of mature oligodendrocytes. This results in defective myelin formation and delayed myelination, causing neurological symptoms. Despite the myelin deficit, most dogs show significant improvement over time, reflecting some remyelination or compensation.
Complications - Puppies affected by hypomyelination manifest with noticeable tremors when awake as early as 2 weeks of age, called "shaking puppies" by breeders. Tremors primarily affect the limbs and head but tend to resolve or significantly improve by 3 to 4 months of age. Some dogs may have a mild persistent tremor, mostly in the hind legs, but most recover to normal or near-normal neurological function.
Why This Matters to Breeders and Vets - The autosomal recessive inheritance means breeders need to be aware of carrier status to avoid breeding two carriers and producing affected puppies. Testing for the FNIP2 mutation allows identification of carriers and affected dogs, supporting responsible breeding to reduce disease incidence while maintaining genetic diversity. Veterinarians can diagnose the condition clinically with confirmation by genetic testing. Understanding this disease helps differentiate it from other causes of tremors or neurological disorders in puppies.
Summary - Brain Hypomyelination in Weimaraners is an autosomal recessive disorder caused by a frameshift mutation in the FNIP2 gene, resulting in defective maturation of oligodendrocytes and reduced myelin formation in the CNS. Clinically, affected puppies exhibit tremors early in life that mostly resolve by a few months of age with minimal lasting effects. Genetic testing enables identification of carriers and management of breeding to reduce disease incidence while maintaining breed diversity.