Table 1.
Overview of mouse models that display features of a syndromic craniosynostosis phenotype
| Gene | Mutation/transgene allele | Human syndrome (OMIM) | Affected sutures | Mechanism | Reference |
|---|---|---|---|---|---|
| Fgf9 | N143T | SYNS3 (612961) | coronal | LOF | Harada et al., 2009 |
| Fgf3 | mutagenesis | Crouzon (123500) | coronal | overexpression | Carlton et al., 1998 |
| Fgf4 | mutagenesis | Crouzon (123500) | coronal | overexpression | Carlton et al., 1998 |
| Fgfr1 | P250R | Pfeiffer (101600) | coronal, interfrontal, sagittal | GOF | Zhou et al., 2000 |
| Fgfr2 | C342Y | Crouzon (123500) | coronal | GOF | Eswarakumar et al., 2004 |
| W290R | Crouzon (123500) | coronal | GOF | Eswarakumar et al., 2004 | |
| S252W | Apert (101200) | coronal, sagittal, lambdoid | GOF | Wang et al., 2005 | |
| S250W | Apert (101200) | coronal, sagittal, lambdoid | GOF | Chen et al., 2003 | |
| Y394C | Beare-Stevenson (123790) | coronal | GOF | Wang et al., 2012 | |
| Fgfr2c | Fgfr2c−/− | NA | coronal | LOF | Eswarakumar et al., 2002 |
| Fgfr2c flox, Fgfr2cflox/− | NA | coronal | LOF | Hajihosseini et al., 2001 | |
| Fgfr2b | Fgfr2b−/− | NA | squamous temporal-parietal | LOF | De Moerlooze et al., 2000 |
| Fgfr3 | P244R | Muenke (602849) | coronal | GOF | Twigg et al., 2009 |
| Twist1 | Twist1+/− | Saethre-Chotzen (101400) | coronal, sagittal, lambdoid | LOF | Chen, 1995; Behr, 2011 |
| Tcf12 | Tcfl2flox/−, Twist1+/−, EIIaCRE/+ | Saethre-Chotzen (101400) | coronal, sagittal, lambdoid | LOF | Sharma et al., 2013 |
| Id1 | Id1+/−, Twist1+/− | Saethre-Chotzen (101400) | coronal, sagittal, lambdoid | LOF | Connerney et al., 2008 |
| Id3 | Id1+/−, Twist1+/− | Saethre-Chotzen (101400) | coronal, sagittal, lambdoid | LOF | Connerney et al., 2008 |
| Msx2 | Timp1-P7H | Boston-type craniosynostosis (604757) | coronal, sagittal, lambdoid | GOF | Liu et al., 1995 |
| CMV-P7H | Boston-type craniosynostosis (604757) | coronal, sagittal, lambdoid | GOF | Liu et al., 1995 | |
| CMV-WT | Boston-type craniosynostosis (604757) | coronal, sagittal, lambdoid | overexpression | Liu et al., 1995 | |
| Jag1 | Jag1+/− | Alagille (118450) | no phenotype | LOF | Yen et al., 2010 |
| Jag1flox/−, Twist1+/−, Mesp1CRE/+ | Alagille (118450) | coronal, sagittal, lambdoid | LOF | Yen et al., 2010 | |
| Gli3 | Gli3Xt-J/Xt-J | Carpenter (201000) | lambdoid | LOF | Hui and Joyner, 1993; Rice et al., 2010 |
| Rab23 | Rab23−/− | Carpenter (201000) | embryonic lethal | LOF | Eggenschwiler et al., 2001 |
| Megf8 | C193R | Carpenter (201000) | sutures not analysed | LOF | Aune et al., 2008 |
| Masp1 | Masp1/3+/− (double KO) | 3MC (257920) | sutures not analysed | LOF | Takahashi et al., 2008 |
| Masp3 | 3MC (257920) | sutures not analysed | LOF | Takahashi et al., 2008 | |
| Hdac4 | Hdac4−/− | Brachydactyly mental retardation (600430) | sutures not analysed | LOF | Vega et al., 2004 |
| Tgfbr1 | M318R | Loeys-Dietz (613795) | coronal | GOF | Gallo et al., 2014 |
| Tgfbr2 | G357W | Loeys-Dietz (613795) | no suture phenotype | GOF | Gallo et al., 2014 |
| Nell1 | WT (CMV) | NA | coronal, sagittal, posterior frontal | overexpression | Zhang et al., 2002 |
| Axin2 | Axin2−/− | NA | coronal, interfrontal | LOF | Yu et al., 2005 |
| Dusp6 | exon 3 STOP, Dusp6+/− | NA | coronal | LOF | Li et al., 2007 |
| Dusp6−/− | NA | coronal | LOF | Li et al., 2007 | |
| Gdf6 | Gdf−/− | NA | coronal | LOF | Settle et al., 2003 |
| Pdgfrα | D846V (R26R) | NA | coronal, interfrontal | overexpression | Moenning et al., 2009 |
| D842V/+, Meox2 CRE/+ | NA | coronal | GOF | He and Soriano, 2017 | |
| D842V/+, Mesp1 CRE/+ | NA | coronal, lambdoid | GOF | He and Soriano, 2017 | |
| EphA4 | EphA4−/− | NA | coronal | LOF | Ting et al., 2009 |
| Twist1+/−, EphA4+/− | NA | coronal | LOF | Ting et al., 2009 | |
| Runx2 | Prx1-Runx2 | NA | pan-synostosis | overexpression | Maeno et al., 2011 |
| Erf | Erf−/− | NA | no phenotype | LOF | Papadaki et al., 2007 |
| Erf flox, Erfflox/+ | NA | no phenotype | LOF | Twigg et al., 2013 | |
| Erf flox, Erfflox/− | NA | coronal, sagittal, lambdoid | LOF | Twigg et al., 2013 | |
| Frem1 | Frameshift (T>C) at intron 25, Frem1 bat/+ | NA | posterior frontal | hypomorph | Smyth et al., 2004 |
| exon 2 deletion, Frem1 QBrick/+ | NA | posterior frontal | LOF | Vissers et al., 2011 | |
LOF, loss of function; GOF, gain of function; NA, not associated (with a human syndrome).