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Enh13 mutant rats for investigation of XX vs. XY differences in phenotypes

Award Number: R21OD042615
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Enh13 mutant rats for investigation of XX vs. XY differences in phenotypes - PROJECT SUMMARY The long-term objectives are to develop and validate rat models of disease that allow investigators to measure the differential effects of XX and XY sex chromosomes that protect from or exacerbate disease. Most human diseases occur differently in males and females, indicating that one sex is protected or vulnerable because of factors that are inherently different in the two sexes. Understanding the mechanisms of protection or vulnerability involves isolating different molecular pathways causing greater or less protection. Sex chromosomes (XX vs. XY) are one major source of sex bias within any type of cell, but this category has been difficult to discriminate from gonadal hormone effects that often co-vary with sex chromosome complement. To isolate and study sex chromosome effects, it is necessary to make experimental models comparing XX and XY animals with the same type of gonad. Such models have not been generally available to investigators who study rats. Rats offer significant advantages as models of human physiology and disease, because of their large size, the large literature concerning basic physiology and sex differences in rats, their superior cognitive ability, and suitability of rats to research on specific diseases. We have developed novel strains with mutations in a specific Sox9 gene enhancer which alters its expression during early gonad development. These modifications allow us to produce XY and XX rats with ovaries, and XX and XY rats with testes. This proposal is to study the newly developed genetically modified rat lines, generate a resource of tissues and transcriptome data to determine how the modifications impact Sox9 gene expression and change the development of ovaries and testes, and to characterize how these mutations alter inducible disease phenotypes known to demonstrate clinical sex differences in humans. These new rat models will be made widely available to investigators interested in studying mechanisms leading to sex differences across a broad range of normal and disease phenotypes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $195,000 )
2026	2026	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Research Infrastructure Programs	001	1	8/21/2026	NEW	-$234,000
2026	2026	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Research Infrastructure Programs	002	1	9/1/2026	NEW	$0
2026	2026	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Research Infrastructure Programs	000	1	8/5/2026	NEW	$429,000
														Subtotal = $195,000

Grand Total All Awards = $195,000

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Enh13 mutant rats for investigation of XX vs. XY differences in phenotypes

Award Number: R21OD042615

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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