Snrnp25 is a candidate for the peri-implantation lethal phenotype of the Hba deletions

Mutations in adult hemoglobin alpha genes in humans lead to blood disorders commonly known as α-thalassemia. In search of a mouse model for this disease, mutagenesis screens have identified several deletions that resemble these phenotypes. The Hba ^b2(th) deletion, in particular, replicates the characteristics of alpha-thalassemia minor in heterozygous mice but presents a homozygous embryonic lethal phenotype. Previous analyses of Hba ^b2(th) mice suggested that the deletion affects both Hba genes ( Hba-a1 and Hba-a2 ) and considered epidermal growth factor receptor ( Egfr ) or rhomboid 5 homolog 1 ( Rhbdf1 ) to be responsible for the embryonic lethality. Molecular analysis of Hba ^b2(th) revealed a deletion spanning a 1cM region of mouse chromosome 11. Importantly, the Hba ^b2(th) deletion does not extend to Egfr , indicating that the observed lethality of homozygous embryos is not due to the loss of Egfr . Sequence analysis of the Hba ^b2(th) deletion showed that the Hba-a2 gene is not deleted, but the lack of expression is likely due to the disruption of upstream regulatory regions. Furthermore, we identify Snrnp2 5, which codes for the small nuclear ribonucleoprotein 25 (U11/U12), as the candidate gene most likely responsible for the peri-implantation lethality of Hba ^b2(th) homozygous mice. These findings enhance the understanding of the genetic mechanisms underlying α-thalassemia and provide insights into novel genes essential for early mammalian development.