# Development of a mouse model of brown fat dystrophia

> **NIH NIH R21** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $238,500

## Abstract

Abstract/Project Summary
Mice physiology is deeply affected by brown fat through its control of metabolic homeostasis and production of
signaling molecules. However, the vast majority of humans do not have brown fat. This deeply bias the use of
mice as a model of human physiology. A mouse model without BAT would allow us to undoubtably determine
the putative roles of brown fat in metabolism, in other organ systems and to have a better, humanized, model
for preclinical research. Following our mechanistic exploration of the role of growth factors/PI3K/mTOR
signaling to understand brown fat formation and metabolism, we unexpectedly generated a mouse model with
no discernable classic brown fat, which we call BAT-less mice. The BAT-less mice are born at normal
mendelian ratios, fully viable, with normal reproductive capacity and the effects are 100% penetrant. Based on
our exciting preliminary data, the central hypothesis for this application is that the complete lack of UCP1
expressing cells in BAT-less mice lead to distinct obesogenic effects compared to UCP1 knockouts. To test
this hypothesis, we have developed a toolkit of unique in vivo models including new reporter mouse models
and a multidisciplinary approach using whole mouse and tissue-clearing lineage tracing techniques, genomics
and state of the art metabolic phenotyping techniques. In Aim 1, we will critically and unequivocally determine if
all brown fat depots are lost in BAT-less at all developmental stages using a multi-reporter system tracking
UCP1 expressing cells. In Aim 2, we will employ the BAT-less mice to test the contribution of BAT energy
consumption to whole body metabolism and obesity propensity independently of UCP1. The BAT-less mice are
anticipated to be useful to scientists in an array of fields with implications in multiple NIH institutes. Additionally,
the BAT-less mice will be a step forward towards a more humanized, broadly useful, mouse model.

## Key facts

- **NIH application ID:** 10450253
- **Project number:** 1R21OD031907-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Juan Sanchez-Gurmaches
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,500
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450253

## Citation

> US National Institutes of Health, RePORTER application 10450253, Development of a mouse model of brown fat dystrophia (1R21OD031907-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10450253. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*