Reep2-flox Mouse

Reep2, a member of the Receptor Expression-enhancing proteins (REEPs) family, is pivotal to the structure and function of the endoplasmic reticulum (ER) [1]. The REEP family is involved in many physiological and pathological processes such as ER morphogenesis, microtubule cytoskeleton regulation, and G protein-coupled receptor (GPCR) trafficking and expression [1]. Reep2 has been found to be preferentially expressed in neuronal and neuronal-like exocytotic tissues including brain, spinal cord, testes, pituitary, and adrenal gland [8].

Mutations in Reep2 have been identified as a cause of "pure" hereditary spastic paraplegias (HSPs), SPG72, with both autosomal dominant and autosomal recessive inheritance [2,5,7]. In a Nepalese family with early-onset pure-type HSP, a heterozygous Reep2 missense mutation (c.119T>G, p.Met40Arg) was found, with the proband presenting a slow and spastic gait from age 2 years [2]. Another study reported a de novo missense mutation (c.119T > G, p.Met40Arg) in a patient with pure hereditary spastic paraplegia [5]. Also, three mutations in Reep2 were identified in two families with HSP, where one missense variant (c.107T>A [p.Val36Glu]) had a dominant-negative effect in the autosomal-dominant family, inhibiting the normal binding of wild-type Reep2 to membranes, and a missense change (c.215T>A [p.Phe72Tyr]) in the recessive family decreased the affinity of the mutant protein for membranes [7]. Additionally, in nasopharyngeal carcinoma, Reep2 was upregulated compared to non-tumor samples, and high expression of Reep2 was associated with poor survival in patients [3]. Moreover, Reep2 enhances sweet receptor function by recruiting them into lipid raft microdomains near the taste cell's apical region, improving G-protein-coupled receptor signaling [4]. Chidamide suppresses adipogenic differentiation of bone marrow-derived mesenchymal stem cells via increasing Reep2 expression, indicating Reep2 is a negative regulator of adipogenic differentiation [6].

In conclusion, Reep2 plays essential roles in multiple biological processes. Its involvement in diseases such as hereditary spastic paraplegias and nasopharyngeal carcinoma, as well as its functions in taste receptor regulation and adipogenic differentiation, are revealed through genetic studies. Understanding Reep2's functions helps in comprehending the pathophysiological mechanisms of related diseases and may provide potential therapeutic targets.