Fmr1, short for Fragile X Messenger Ribonucleoprotein 1, is a gene of great significance. The encoded protein, fragile X mental retardation protein (FMRP), is proposed to act as a regulator of mRNA transport and translation of target mRNAs at the synapse [5]. It is involved in multiple biological processes and is associated with several disorders.

Fmr1 is closely related to Fragile X syndrome (FXS), which is the most common inherited form of intellectual disability. Usually, it is due to CGG-repeat expansions in the FMR1 gene leading to lack of expression [1]. Rare missense or nonsense mutations or other coding disturbances of the FMR1 gene can also cause FXS-like features, such as intellectual disability, autism, and hyperactivity [1]. In FXS, the FMR1 gene may be transcribed, but its RNA is mis-spliced in a CGG expansion-dependent manner, generating the FMR1-217 RNA isoform, and antisense oligonucleotide treatment can rescue full-length FMR1 RNA and restore FMRP [2]. Expansions of the CGG repeat in the 5' untranslated region of FMR1 can also lead to premature ovarian failure type 1 (POF1) in heterozygous females when the repeat number is between 55 and 200, known as a fragile X premutation [4]. FMR1 premutation carriers are also at risk of developing Fragile X-associated tremor/ataxia syndrome (FXTAS) in adulthood [3].

In conclusion, Fmr1 plays a crucial role in mRNA regulation at the synapse. Studies on Fmr1-related mouse models would likely provide insights into how disruptions in this gene lead to FXS, POF1, and FXTAS, helping to understand the underlying disease mechanisms and potentially develop therapeutic strategies for these disorders.