NOD/ShiLt-Tg(H2-Ea^d)12Lt/J

Stock number: 002035
Product name: NOD-Eα^d line 12
Research areas: Diabetes and Obesity Research

Description

These NOD-Ea^d line 12 mice express a transgene containing a construct of the complete H2-Ea^d gene from BALB/cByJ. Diabetes incidence in this strain is reduced while H2-Ea expression is comparable to BALB/cByJ controls.

Detailed description

A requirement for developing insulin-dependent diabetes mellitus (IDDM) in mice is the absence of functional H2-Ea and H2-Ab1 genes. NOD/Lt mice (H2^g7 = K^d, A^g7, E^null, D^b) fulfill this requirement and develop IDDM. Two homozygous transgenic lines (NOD/ShiLt-Tg(H2-Ea^d)5Lt/J (Stock No. 002034) commonly referred to as line 5; and NOD/ShiLt-Tg(H2-Ea^d)12Lt/J (Stock No. 002035), referred to as line 12) were created to further examine the quantitative thresholds of MHC class II expression and the mechanisms involved in preventing IDDM development in NOD mice. These strains harbor a construct containing a complete H2-Ea^d gene from BALB/cByJ mice. Only a single copy of the Ea^d transgene integrated into the genome of line 12 where as four copies are present in line 5. Diabetes incidence in line 12 is greatly reduced (25% of females, 0% of males) where H2-Ea expression on antigen presenting cells is comparable to BALB/cByJ controls. Overexpression of H2-Ea in line 5 confers nearly complete resistance to IDDM. Although the presence of the Ea^d transgene in both lines confers protective influence from IDDM pathologies that affect pancreatic beta cells, autoimmune pathologies effecting other tissues (submandibular salivary, thyroid, kidney) are observed. Histologic examination of thepancreas reveals perivascular/periductal infiltration and peri-insulitus.

Development

A 14 kb XhoI-SacII fragment containing the H2-Ea gene and flanking sequences was isolated from a cosmid of BALB/c origin and utilized in a transgenic construct. The construct was injected into NOD/Lt zygotes. Two founder lines resulted (Stock Nos. 002034 and 002035).

Allele

Symbol: Tg(H2-Ea^d)12Lt
Name: transgene insertion 12, Edward H Leiter
MGI accession ID: MGI:3052550
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(H2-Ea^d)12Lt
Marker name: transgene insertion 12, Edward H Leiter
Chromosome: UN
Strain of origin: NOD/ShiLt
Expressed genes: H2-I,H2 I region, includes H2-Aa, Ab, Bl, Ea, Eb, Eb2, Ob, Pb,mouse, laboratory
Molecular note: The construct contains a complete H2-Ea^d gene from the BALB/cByJ mouse including flanking sequence. One copy of the transgene integrated into the genome of line 12 whereas four copies are present in line 5.
General note: Diabetes incidence in transgenic mice carrying line 12 is greatly reduced (25% of females, 0% of males) where H2-Ea expression on antigen presenting cells is comparable to BALB/cByJ controls. Although the presence of the transgene in both lines 5 and 12 confers protective influence from IDDM pathologies that affect pancreatic beta cells, autoimmune pathologies effecting other tissues (submandibular salivary, thyroid, kidney) are observed. Histologic examination of the pancreas reveals perivascular/periductal infiltration and peri-insulitus.