HNF1β-associated cyst development and electrolyte disturbances are not explained by BAIAP2L2 expression

Area of Science:

• Molecular Biology
• Genetics
• Nephrology

Background:

• Mutations in hepatocyte nuclear factor 1 homeobox β (HNF1β) are linked to renal cysts, diabetes, and electrolyte imbalances.
• Understanding HNF1β's transcriptional targets is crucial for explaining its kidney-related phenotypes.

Purpose of the Study:

• To identify novel transcriptional targets of HNF1β using bioinformatic analysis.
• To investigate the role of BAR/IMD Domain Containing Adaptor Protein 2 Like 2 (BAIAP2L2) in kidney epithelial cell integrity and function.

Main Methods:

• Comprehensive bioinformatic analysis of ChIP-seq, RNA-seq, and gene expression array data.
• Reporter luciferase assay to validate HNF1β-mediated transcriptional activation of BAIAP2L2.
• Mass spectrometry to identify BAIAP2L2 interacting proteins.
• Baiap2l2 knockout cell and mouse models to assess in vitro and in vivo function.

Main Results:

• BAR/IMD Domain Containing Adaptor Protein 2 Like 2 (BAIAP2L2) was identified as a novel transcriptional target of HNF1β.
• BAIAP2L2 directly activates the BAIAP2L2 promoter and interacts with other I-BAR domain proteins (BAIAP2, BAIAP2L1).
• Loss of BAIAP2L2 in kidney epithelial cells did not affect F-actin distribution or spheroid formation.
• Baiap2l2 knockout mice exhibited normal kidney and colon morphology, with unaffected electrolyte homeostasis.

Conclusions:

• BAIAP2L2 is a novel transcriptional target of HNF1β.
• Despite its identification as a target, BAIAP2L2 does not appear to play a critical role in maintaining kidney epithelial cell integrity or electrolyte homeostasis under physiological conditions.
• This study provides the first in vivo characterization of BAIAP2L2 function in the kidney.