PTEN mutant animal models have been extensively studied across the academic community and others, with conditional PTEN knock-out models having been developed for several different tissue types. Each of these models has shown varied phenotypic outcomes and have provided insight into the broad functional role of PTEN highlighting its importance for normal tissue function. Many of these models, although not all, are commercially available. Included here are the mouse models that have been utilised in studies funded by PTEN Research.
In addition, PTEN Research is supporting the generation of new PTEN mutant animal models. Information regarding these models is not currently available, however, this page will be updated once these models are developed and available.
Please note that this is not a comprehensive list of all the available models, and there may be other tools that are more suitable to your research needs, each of which have their own advantages and disadvantages.
The Vanhaesebroeck laboratory at University College London (UK) has generated a Pten+/R173C missense mutation mouse and characterised this model in collaboration with other research groups. The PTEN-R173C mutation is commonly observed in somatic tumours, and has been reported in patients diagnosed with PHTS (ClinVar Variation ID: 189500).
PTEN-R173C has reduced protein stability but retains its ability to dephosphorylate PIP3 and therefore regulate the canonical PI3K/AKT pathway in the cytosol. However, this PTEN mutant is largely excluded from the nucleus. In a systemic, germline heterozygous context the R173C mutation is not a strong driver for tumour development, but results in macrocephaly and lymphadenopathy.
This project received funding from PTEN Research.
This mouse model can be obtained from the European Mouse Mutant Archive (EMMA; ID 14917).
The Sahin laboratory at the Boston Children’s Hospital, US, have generated and characterised a novel neuron-specific Pten knock-out mouse model (Syn-Cre;Ptenf/f). These animals show an increased brain:body weight ratio and shortened lifespan as well as neurological phenotypes relevant to PHTS, such as synaptic and neuronal activity alterations, which are responsive to treatment with mTOR inhibitors. Molecular analysis data, including transcriptomic profiling, is also available for this model.
This project received funding from PTEN Research.
This mouse model can be requested from Mustafa.Sahin@childrens.harvard.edu.
The Graupera laboratory at the Institute Josep Carreras (Spain) generated and used inducible endothelial cell-specific Pten knock-out mouse models (Cdh5-CreERT2;PtenKO/EC and Pdgfb-CreERT2;PtenKO/EC) to investigate the role of PTEN loss in the development of both lymphatic and blood vascular malformations. Imaging and molecular data documenting the characterisation of these models are also available.
Three separate laboratories generated three alternative PTEN germline heterozygous knock-out mouse models that have been extensively studied in the context of the implications of systemic heterozygous PTEN loss (Di Cristofano et al., 1998; Suzuki et al., 1998; Podsypanina et al., 1999). These models are useful tools to study PHTS, as they partially phenocopy the patient condition, with development of tumours and macrocephaly.
Using one of these lines, the Vanhaesebroeck laboratory at University College London (UK) showed that long-term treatment with the mTORC1 inhibitor rapamycin delays tumour development in these mice. This project received funding from PTEN Research.
