# Molecular Genetics Core

> **NIH NIH P30** · YALE UNIVERSITY · 2023 · $96,944

## Abstract

The overall goal of this Core is to support and advance diabetes-related research through the generation
of unique, genetically-modified mutant mouse models. We currently provide a number of highly specialized
services contained within two tightly integrated Subcores: 1) the Molecular Subcore designs and generates
gene expression constructs and CRISPR tools for genetic modification in mice and cultured cell lines, provides
genotyping design/ mutation characterization, gene mapping/ localization and the quantitation of gene
expression by quantitative RT-PCR, and 2) the Gene Targeting Subcore generates genetically-modified mouse
models in a variety of standard strains (such as C57BL/6, Balb/c, etc.) and specialized genetic backgrounds
(including NOD and various immunodeficient strains, such as Rag/Il2rg KOs) via CRISPR/Cas9 approaches,
conventional transgenesis and ES cell recombination methods, and also provides sperm cryopreservation and
IVF recovery of preserved strains. The specific aims of the Molecular Genetic Mouse Core are therefore to
provide the following: a) critical services, b) technical assistance, c) experimental design, consultation/ advice,
troubleshooting, d) training and e) equipment and resources, centered around the generation of genetically-
modified mouse models by a variety of both traditional and CRISPR-related methods, including knock-outs,
conditional knockouts, inducible knockouts, conditional gene activation, and a variety of knock-ins (tags,
reporters, mutations and exon/domain or whole gene replacements).
 The MGM Core has successfully generated a great many lines of genetically-modified mice related to
diabetes studies, most recently using CRISPR-based technology, and its continuing focus on technological
development will ensure that services to the diabetes community remain cutting-edge. In addition, a unique
feature of this core is that the interests of the subcore directors have fueled a critical mass of resources for
investigation of the rapidly developing research areas of the mechanistic relationships between gut microbiota,
inflammasome biology and obesity, NAFLD, and type 1 and type 2 diabetes. The MGM Core has developed
mouse models with ablated or altered genes involved in regulation of the innate immune system, including
NOD-like receptor proteins, Toll-like receptors, guanylate binding proteins, the apolipoprotein L family, and
various interleukins and caspases. Finally, the core has a continuing investment in extending and improving
the development and application of technologies for humanization of the mouse genome for engraftment of
CD34+ human HSC, and the reconstitution of a human hematopoietic and immune system. These “humanized”
mouse models will be invaluable tools for the dissection of the genetic components regulating the immunologic
and metabolic responses in both type 1 and type 2 diabetes, especially with respect to human disease.

## Key facts

- **NIH application ID:** 10588656
- **Project number:** 2P30DK045735-31
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Richard A Flavell
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $96,944
- **Award type:** 2
- **Project period:** 1997-01-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10588656

## Citation

> US National Institutes of Health, RePORTER application 10588656, Molecular Genetics Core (2P30DK045735-31). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10588656. Licensed CC0.

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