# Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division

## TL;DR

Mice with only one CDK2 isoform can still undergo normal cell division, showing the two isoforms can replace each other.

## Contribution

Generated mice expressing only one CDK2 isoform to show functional redundancy in mitotic and meiotic division.

## Key findings

- Mice with only CDK2S or CDK2L are viable and fertile.
- Both CDK2 isoforms can support mitotic and meiotic division alone.
- CDK2 isoforms show overlapping functions despite differing kinase activity.

## Abstract

In most mammals, the cell cycle kinase cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms as a result of alternative splicing. The shorter CDK2 isoform, CDK2S, is expressed constitutively during the cell cycle and can be detected in several tissues. In contrast, the longer isoform, CDK2L, shows preferential expression in meiotically dividing cells and upon S-phase entry in the mitotic cycle. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1 in vitro. However, complexes composed of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different roles in vivo during either mitotic or meiotic divisions as conventional knockout methodology deletes both of the isoforms. Therefore, we generated mice expressing only CDK2S or CDK2L and found that both CDK2L and CDK2S are sufficient to support both mitotic and meiotic division when expressed in the absence of the other. These data contribute to the explanation of the apparent tolerance of the evolutionary loss of CDK2L expression in humans.

Summary: Mice expressing only one of the CDK2S or CDK2L isoforms are viable and fertile, in contrast to Cdk2 knockout mice, showing that these isoforms have overlapping functions and can compensate for each other.