A point mutation in an otherwise dispensable upstream Fshb enhancer moderately impairs fertility in female mice

Follicle-stimulating hormone (FSH) is necessary for fertility in both sexes as a regulator of gametogenesis and hormone synthesis. Humans with loss-of-function mutations within the gene encoding the FSH beta subunit (FSHB) are infertile. Similarly, female Fshb knock-out mice are infertile and fail to ovulate, and males are subfertile. We recently reported the discovery and characterization of an upstream enhancer of FSHB located 26 Kb upstream of the transcriptional start site in humans (-17 Kb in mouse) that also amplifies activin and gonadotropin-releasing hormone induction of FSHB. Notably, the upstream enhancer contains a polymorphic, fertility-associated site in humans, rs11031006 (G/A), and the minor allele (A) increased enhancer activity in vitro as compared to the major allele (G), likely by increasing the affinity of an SF1 binding element. To investigate the role of the novel enhancer and rs11031006 variant in vivo, we created mouse models to assess deletion of the upstream en..., , # Fertility is impaired by a point mutation in an upstream Fshb enhancer in female mice

Dataset DOI: [10.5061/dryad.7h44j105w](10.5061/dryad.7h44j105w)

## Description of the data and file structure

In this study, we created mouse models to evaluate the role of the -17 Kb *Fshb* enhancer and the rs11031006 variant. Overall, we evaluated reproduction in three mouselines:

FshbeΔ777: 777 bp deletion encompassing the enhancer region located 17 Kb upstream of the *Fshb* TSS (chr2:107,076,836-107,077,614, mm10).

FshbeΔ6kb: A 6 Kb deletion including the enhancer at 17 Kb and the C2 element at 12 Kb (deletion of chr2:107,071,698-107,078,356, mm10).

SNP06_G>A: G>A point mutation at the genomic position equivalent to the human rs11031006(G/A) single nucleotide polymorphism (chr2:107,077,053, mm10).

### Files and variables

#### File: Supplemental\_Dryad.pdf

**Description:** Graphical representations of data. All data necessary to support the research findings in this supplement are include...,