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Published on: April 2, 2020
Grb7 knockout mice develop normally but litters born to knockout females fail to thrive
Kristopher A Lofgren1, Paraic A Kenny1,2
1Kabara Cancer Research Institute, Gundersen Medical Foundation, La Crosse, Wisconsin, USA.
Background:
Growth factor receptor-bound 7 (Grb7) is an adaptor protein involved in signal transduction downstream of multiple receptor tyrosine kinases, including ERBB, FGFR, and PDGFR pathways. Experimental studies have implicated Grb7 in regulating cell proliferation, survival, migration, and invasion through its large repertoire of protein-protein interactions.
Results:
Here, we describe the generation and characterization of a Grb7 knockout mouse. These mice are viable and fertile. A lacZ knock-in reporter was used to visualize Grb7 promoter activity patterns in adult tissues, indicating widespread Grb7 expression in glandular epithelium, the central nervous system, and other tissues. The sole defect observed in these animals was a failure of Grb7 knockout females to successfully raise pups to weaning age, a phenotype that was independent of both paternal and pup genotypes.
Conclusions:
These data suggest a regulatory role for Grb7 in mammary lactational physiology.
Insights
Growth factor receptor-bound 7 (Grb7) is crucial for mammary gland function. Grb7 knockout females exhibit impaired pup-rearing, indicating its role in lactational physiology.
Area of Science:
- Molecular Biology
- Genetics
- Physiology
Background:
- Growth factor receptor-bound 7 (Grb7) is an adaptor protein.
- Grb7 participates in signal transduction pathways including ERBB, FGFR, and PDGFR.
- It regulates cell proliferation, survival, migration, and invasion via protein interactions.
Purpose of the Study:
- To generate and characterize a Grb7 knockout mouse model.
- To investigate the in vivo function of Grb7.
- To understand Grb7's role in physiological processes.
Main Methods:
- Generation of Grb7 knockout mice.
- Characterization of mouse viability and fertility.
- Use of a lacZ knock-in reporter to assess Grb7 expression patterns.
- Phenotypic analysis of Grb7 knockout females regarding pup rearing.
Main Results:
- Grb7 knockout mice are viable and fertile.
- LacZ reporter revealed widespread Grb7 expression in adult tissues, notably glandular epithelium and CNS.
- Grb7 knockout females failed to successfully raise pups to weaning age.
- This reproductive defect was independent of paternal and pup genotypes.
Conclusions:
- Grb7 plays a significant role in mammary lactational physiology.
- The study highlights a specific function of Grb7 in maternal care and offspring survival.
- Further research can explore the precise molecular mechanisms underlying Grb7's function in lactation.
