B6.129P2-Dp(16Lipi-Zbtb21)1TybEmcf/J

Stock number: 037183
Product name: Dp1Tyb
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Dp(16Lipi-Zbtb21)1TybEmcf (Dp1Tyb) mice contain a 23 Mb duplication that extends from the lipase, member I (Lipi) gene to the zinc finger and BTB domain containig 21 (Zbtb21) on mouse chromosome 16. The region includes 148 coding genes and is orthologous to human chromosome 21, covering about 65% of Hsa21. Dp1Tyb mice carry three copies of all 148 genes. Hemizygous mice exhibit multiple pathologies associated with Down Syndrome including cardiac defects, craniofacial defects, locomotor defects, memory defects, and sleep alterations.

Detailed description

Dp(16Lipi-Zbtb21)1TybEmcf (Dp1Tyb) mice carry a duplication of the region from lipase, member I (Lipi) gene to the zinc finger and BTB domain containig 21 (Zbtb21) on mouse chromosome 16. The region spans 23 Mb and includes 148 coding genes (GRCm38). This region is orthologous to 65% of human chromosome 21 and is associated with Down Syndrome. Hemizygous Dp1Tyb mice are viable and fertile and carry three copies of all 148 genes. Homozygous mice have not been generated. The mutation breeds equally well from male and female mice, however, the yield of Dp1Tyb pups at weaning is reduced to 33% (vs 50%) of numbers expected from Mendelian ratios. E14.5 day Dp1Tyb embryos have multiple congenital heart defects including abnormal arterial trunk arrangements (18%), ventricular septal defects (62%), and atrio-ventricular septal defects (25%). In addition, hemizygous Dp1Tyb mice exhibit locomotor dysfunction (Watson-Scales et al 2018; PMID: 29746474), altered gene expression (Ahlfors et al; PMID:31171815), deficits in bone mineral density and trabecular architecture (Thomas et al 2020; PMID: 32305495), impaired decision making (Chang et al 2020; PMID: 31995755), craniofacial defects (Toussaint et al 2021; PMID:33712441), sleep alterations, impaired hearing, increased megakaryopoiesis and a pre-diabetic state (Lana-Elola et al 2021; PMID: 34477842).

These mice may be useful in studies of Down Syndrome (DS).

Development

MICER vectors MHPP352i17 (coordinates of homology region 16:74930370-16:74937378 Mb; mouse assembly GRCm38/mm10) and MHPN352i16 (16:97977263-16:97982380 Mb) were used as targeting vectors to insert loxP sites proximal to Lipi and distal to Zbtb21 on chromosome 16. The region includes 148 coding genes and is 23 Mb in length (GRCm38). The construct was electroporated into 129P2/OlaHsd-derived HM-1 embryonic stem (ES) cells. Cre recombinase was transiently expressed in ES cells to duplicate the region flanked by loxP sites. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6JNimr females. Segmental duplication was confirmed by Southern blot analysis. Mice were backcrossed to C57BL/6JNimr for more than 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Dp(16Lipi-Zbtb21)1TybEmcf
Name: duplication, Chr 16, Victor Tybulewicz and Elizabeth M C Fisher 1
MGI accession ID: MGI:5703798
Generation method: Targeted
Synonyms: Dp(16)1TybEmcf; Dp1Tyb
Marker symbol: Dp(16Lipi-Zbtb21)1TybEmcf
Marker name: duplication, Chr 16, Victor Tybulewicz and Elizabeth M C Fisher 1
Chromosome: 16
Strain of origin: 129P2/OlaHsd-Hprt1^b-m3
Molecular note: MICER vectors MHPP352i17 (coordinates of homology region 16:74930370-16:74937378 Mb; mouse assembly GRCm38/mm10) and MHPN352i16 (16:97977263-16:97982380 Mb) were used to insert loxP sites proximal to Lipi and distal to Zbtb21. Cre-mediated recombination duplicated the 23 Mb floxed by loxP sites.