Fibroblast Growth Factor 4, or FGF4, is a protein that plays a role in numerous biological processes across different species. FGF4 contributes to growth and development by influencing cell proliferation, differentiation, and survival.
FGF4’s Role in Canine Physical Traits
Variations within the FGF4 gene are responsible for several distinct physical characteristics observed in dogs. One prominent example is chondrodysplasia, a condition characterized by shortened limbs, often referred to as dwarfism, seen in breeds like Dachshunds, Corgis, and Basset Hounds. This short-legged phenotype is linked to a specific FGF4 retrogene insertion on canine chromosome 18 (CFA18).
A retrogene is a functional copy of a gene that has been reinserted into the genome at a different location. The FGF4 retrogene on CFA18 is believed to cause chondrodysplasia by disrupting normal bone development, leading to early calcification of growth plates and consequently shortened, sometimes curved, long bones. This particular retrogene is fixed in at least 15 chondrodysplastic breeds, meaning it is present in nearly all individuals of those breeds.
Another FGF4 retrogene insertion, located on canine chromosome 12 (CFA12), also contributes to a short-legged phenotype, known as chondrodystrophy, and can influence other traits. This variant is found in breeds such as French Bulldogs, Beagles, and Dachshunds. Beyond limb length, this CFA12 FGF4 retrogene has also been associated with variations in coat length, such as the “fluffy” or long-haired trait observed in some French Bulldogs. Genetic tests are available for these FGF4 variants, allowing breeders and owners to understand the genetic makeup of their dogs regarding these traits.
Understanding FGF4’s Biological Function
FGF4 is a member of the fibroblast growth factor family, a diverse group of signaling molecules that regulate a wide array of biological functions. These functions include cell growth, differentiation, and tissue repair in many species, including humans and dogs. FGF4 operates by binding to specific receptors located on the surface of cells, initiating a cascade of internal events that lead to various cellular responses.
The protein plays a role in embryonic development, guiding the formation of organs and limbs. For instance, FGF4 is involved in the proper development of cardiac valves and limbs during embryogenesis. It contributes to the survival and growth of the inner cell mass in the early stages of development.
Health Implications and FGF4
Variations in FGF4, particularly the retrogene on canine chromosome 12 (CFA12), have health implications for dogs. This specific retrogene is linked to an increased risk of intervertebral disc disease (IVDD) in short-legged breeds, including Dachshunds, French Bulldogs, and Beagles. IVDD in these breeds results from the premature degeneration and calcification of intervertebral discs, which can lead to disc herniation and subsequent pain or paralysis.
The presence of one or two copies of the CFA12 FGF4 retrogene can increase the risk of disc herniation and lead to a younger age of onset for IVDD. Beyond canine health, FGF4 and its related receptors are subjects of human health research, with investigations into their involvement in certain cancers and their potential as therapeutic targets. For example, elevated levels of Fibroblast Growth Factor Receptor 4 (FGFR4), a receptor for FGF4, have been associated with the development and progression of various solid tumors.