Table 2.
Mouse models of pituitary neoplasia.
| Tumour type | Tumour site | Syndrome/Disorder | Mouse model (gene – method) | Gender phenotype | Reference |
|---|---|---|---|---|---|
| Prolactinoma (secreting prolactin) | Isolated | Carney Complex |
Prkar1a – Tissue-specific homozygous knockout |
__ | (Yin et al., 2008) |
| Acromegaly/ Gigantism |
Ghrh – Transgenic over-expression |
__ | (Asa et al., 1992a, Asa et al., 1992b) | ||
| Non-syndromic |
Prl – Heterozygous and homozygous knockout |
Female only | (Cruz-Soto et al., 2002) | ||
|
Prlr – Homozygous knockout |
Male and female | (Schuff et al., 2002) | |||
|
TGFα - Tissue-specific transgenic Over-expression |
Females only | (McAndrew et al., 1995) | |||
|
ptd-FGFR4 – Tissue-specific transgenic Over-expression |
Male and female | (Ezzat et al., 2002) | |||
|
Prop1 – Tissue specific transgenic Over-expression |
Female only | (Egashira et al., 2008, Cushman et al., 2001) | |||
|
Drd2 – Homozygous knockout |
Females only | (Kelly et al., 1997, Asa et al., 1999) | |||
|
Cyclin E – Tissue-specific transgenic over-expression |
__ | (Roussel-Gervais et al., 2010) | |||
| Multiple | MEN1 |
Men1 – Heterozygous knockout |
Higher incidence in females | (Crabtree et al., 2001, Bertolino et al., 2003a, Bertolino et al., 2003b, Biondi et al., 2002, Loffler et al., 2007a, Loffler et al., 2007b, Harding et al., 2009, Lemos et al., 2009) | |
|
Men1 – Tissue-specific homozygous knockout |
Higher incidence in females | (Biondi et al., 2004, Crabtree et al., 2003) | |||
| Non-syndromic |
Pttg:Rb – Tissue-specific transgenic Pttg over-expression: Heterozygous Rb knockout |
Male and female NB Pttg knockout x Rb knockout is protective for pituitary adenomas |
(Donangelo et al., 2006, Chesnokova et al., 2005) | ||
|
p19 – Homozygous knockout |
Male and female | (Bai et al., 2014) | |||
|
Hmga1 – Transgenic over- expression |
Higher incidence in females | (Fedele et al., 2005) | |||
|
Hmga2 – Transgenic over- expression |
Higher incidence in females | (Fedele et al., 2002) | |||
|
AVP-SV40 large T antigen – Transgenic expression |
__ | (Stefaneanu et al., 1992) | |||
| Gonadotrophinoma (secreting follicle stimulating hormone, lutenising hormone, or non-functioning) | Isolated | Non-syndromic | FSHβ-SV40 temperature sensitive T antigen –Transgenic expression | Male only | (Kumar et al., 1998) |
|
Pttg – Tissue-specific transgenic over-expression |
Male and Female | (Donangelo et al., 2006, Abbud et al., 2005) | |||
|
Prop1 – Tissue-specific transgenic Over-expression |
Female only | (Egashira et al., 2008, Cushman et al., 2001) | |||
|
Cyclin E – Tissue-specific transgenic over-expression |
__ | (Roussel-Gervais et al., 2010) | |||
| Multiple | MEN1 |
Men1 – Heterozygous knockout |
Higher incidence in females | (Crabtree et al., 2001, Bertolino et al., 2003a, Bertolino et al., 2003b, Biondi et al., 2002, Loffler et al., 2007a, Loffler et al., 2007b, Harding et al., 2009, Lemos et al., 2009) | |
| Non-syndromic |
Pttg:Rb – Tissue-specific transgenic Pttg over-expression: Heterozygous Rb knockout |
Male and female NB Pttg knockout x Rb knockout is protective for pituitary adenomas |
(Donangelo et al., 2006, Chesnokova et al., 2005) | ||
|
p19 – Homozygous knockout |
Male and female | (Bai et al., 2014) | |||
| Somatotrophinoma (secreting growth hormone) | Isolated | FIPA |
Aip – Heterozygous knockout |
Male and female | (Raitila et al., 2010) |
| Carney Complex |
Prkar1a – Tissue-specific homozygous knockout |
__ | (Yin et al., 2008) | ||
| Acromegaly/ Gigantism |
Ghrh – Transgenic over- expression |
__ | (Asa et al., 1992a, Asa et al., 1992b) | ||
| Non-syndromic |
Prop1 – Tissue-specific transgenic over-expression |
Female only | (Egashira et al., 2008, Cushman et al., 2001) | ||
|
Cyclin E – Tissue-specific transgenic over-expression |
__ | (Roussel-Gervais et al., 2010) | |||
| Multiple | MEN1 |
Men1 – Heterozygous knockout |
Higher incidence in females | (Crabtree et al., 2001, Bertolino et al., 2003a, Bertolino et al., 2003b, Biondi et al., 2002, Loffler et al., 2007a, Loffler et al., 2007b, Harding et al., 2009, Lemos et al., 2009) | |
| Non-syndromic |
Pttg:Rb – Tissue-specific transgenic Pttg over-expression: Heterozygous Rb knockout |
Male and female NB Pttg knockout x Rb knockout is protective for pituitary adenomas |
(Donangelo et al., 2006, Chesnokova et al., 2005) | ||
|
p19 – Homozygous knockout |
Male and female | (Bai et al., 2014) | |||
|
Hmga1 – Transgenic over- expression |
Higher incidence in females | (Fedele et al., 2005) | |||
|
Hmga2 – Transgenic over- expression |
Higher incidence in females | (Fedele et al., 2002) | |||
|
AVP-SV40 large T antigen – Transgenic over-expression |
__ | (Stefaneanu et al., 1992) | |||
| Corticotrophinoma (secreting adrenocorticotropic hormone) | Isolated | Acromegaly/ Gigantism |
p18 – Homozygous knockout |
Male and female | (Franklin et al., 1998) |
|
p18:p27 – Homozygous p18 knockout: Homozygous p27 knockout |
Male and female Accelerated rate of adenomas |
(Franklin et al., 1998) | |||
| Cushing's |
PyLT – Transgenic over- expression |
Male and female | (Helseth et al., 1992) | ||
|
Crh – Transgenic over- expression |
Male and female | (Stenzel-Poore et al., 1992) | |||
|
Crh – Heterozygous gain-of-function mutation (ENU) |
Male and female | (Bentley et al., 2014) | |||
| Non-syndromic |
Pttg:Rb – Tissue-specific transgenic Pttg over-expression: Heterozygous Rb knockout |
Male and female NB Pttg knockout x Rb knockout is protective for pituitary adenomas |
(Donangelo et al., 2006, Chesnokova et al., 2005) | ||
| Multiple | Non-syndromic |
Rb:Ini1 – Heterozygous Rb knockout: Heterozygous Ini1 knockout |
__ Accelerated carcinoma development |
(Guidi et al., 2006) | |
| SV40 large T antigen –Transgenic expression under Pomc promoter | __ | (Low et al., 1993) | |||
|
AVP-SV40 large T antigen – Transgenic over- expression |
__ | (Stefaneanu et al., 1992) | |||
| Thyrotrophinoma (secreting thyroid stimulating hormone) | Isolated | Carney Complex |
Prkar1a – Tissue-specific homozygous knockout |
__ | (Yin et al., 2008) |
| Acromegaly/ Gigantism |
Ghrh – Transgenic over- expression |
__ | (Asa et al., 1992a, Asa et al., 1992b) | ||
| Non-syndromic |
p18:αSU – Homozygous p18 knockout: Homozygous αSU knockout |
__ | (Lloyd et al., 2002) | ||
|
Prop1 – Tissue-specific transgenic over-expression |
Female only | (Egashira et al., 2008, Cushman et al., 2001) | |||
| Multiple | Non-syndromic |
AVP-SV40 large T antigen – Transgenic over- expression |
__ | (Stefaneanu et al., 1992) | |
| Craniopharyngiomas | Isolated | Non-syndromic |
Ctnnb1 – Tissue-specific knockout of exon 3, rendering Ctnnb1 degradation resistant |
__ | (Gaston-Massuet et al., 2011) |
| Undefined adenoma subtype | Isolated | Non-syndromic |
Bmi1 – Tissue-specific transgenic over-expression |
__ | (Westerman et al., 2012) |
| Multiple | MEN4 |
Cdkn1b – Homozygous knockout |
Male and female - females infertile | (Kiyokawa et al., 1996, Nakayama et al., 1996, Fero et al., 1996) | |
|
Cdkn1b – Homozygous inactivating mutation knockin |
__ | (Besson et al., 2006) | |||
| Non-syndromic |
Cdk4 – mutation (rendering protein insensitive to INK4 inhibitors) knockin |
Male and female | (Sotillo et al., 2001) | ||
| Cdk4:Cdkn1b – Transgenic Cdk4 mutation knockin: Homozygous Cdkn1b knockout | __ | (Sotillo et al., 2005) | |||
|
Men1:Cdk2 – Heterozygous Men1 knockout: homozygous Cdk2 knockout |
Male and female | (Gillam et al., 2015) | |||
|
Cyclin E:p27 – Tissue-specific transgenic Cyclin E over-expression: Homozygous p27 knockout |
__ Increased adenoma size, proliferation and frequency |
(Roussel-Gervais et al., 2010) | |||
|
Ink4c:Arf – Homozygous Ink4c knockout: Homozygous Arf knockout |
Male and female | (Zindy et al., 2003) | |||
|
Rb – Heterozygous knockout |
__ | (Jacks et al., 1992) | |||
|
Rb – Tissue-specific homozygous knockout |
__ | (Vooijs et al., 1998, Vooijs et al., 2002) | |||
|
Rb:Arf – Heterozygous Rb knockout: Homozygous Arf knockout |
__ Accelerated tumour development |
(Tsai et al., 2002) | |||
|
Rb:p53 – Heterozygous Rb knockout: Heterozygous and homozygous p53 knockout |
__ | (Harvey et al., 1995) |
- = not defined; MEN1 – multiple endocrine neoplasia type 1; MEN4 - multiple endocrine neoplasia type 4; FIPA – familial isolated pituitary adenomas.