# Roles of X- and Y-palindromic Genes in Mammalian Fertility

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $336,354

## Abstract

Project Summary
Mammalian sex chromosomes are enriched with large palindromic sequences harboring gene families
expressed almost exclusively in spermatogenic cells, however the molecular functions of these palindromic
genes remain largely unknown. Understanding the mechanistic functions of individual palindromic gene
families will provide novel insights into genetic factors that contribute to spermatogenic defects (abnormalities
in the development of testicular germ cells). The objective of this proposal is to precisely delete individual X-
and Y-palindrome gene families to determine their molecular functions during spermatogenesis. This proposal
addresses whether deletion of all copy members of an individual X- or Y-palindromic gene family results in
spermatogenic defects. This proposition is based on the observation that deletions that remove all members of
X- or Y-palindromic gene families result in spermatogenic defects. However, each of these previously studied
deletions remove more genes than just an individual palindromic gene family, making it difficult to determine
the contribution of individual palindromic gene families to spermatogenic defects. Therefore, we propose to
generate precise deletions that remove all members of individual X- or Y-palindromic gene families in mice to
understand their role in spermatogenesis. As proof of feasibility, we have generated two, independent,
megabase-sized deletions of the Slx and Slxl1 X-palindromic gene families and show that male mice carrying
deletions of both gene families are infertile, exhibiting a specific post-meiotic spermatogenic defect (Preliminary
Studies). This proposal addresses the importance of X- and Y-palindromic genes via two specific aims: 1)
Determine the role of the Slx and Slxl1 X-palindromic gene families in post-meiotic spermatogenesis in male
mice carrying deletions of both the Slx and Slxl1 palindrome arrays; 2) Determine the contribution of four
additional X- and Y-palindromic gene families in spermatogenesis by individually deleting each of the four
distinct gene families. To genetically dissect the functions of individual X- and Y-palindromic gene families in
mice, we have developed new chromosome engineering methodologies to efficiently delete large palindromic
regions in vivo. Each of the X- and Y-palindromic gene families in mice will be systematically characterized for
defects in spermatogenesis. The functions of individual X- and Y-palindromic gene families have been poorly
studied in humans and mice because of their recent discovery and complex genomic architecture. The
proposed experiments will provide an improved understanding of the roles of individual X- and Y-palindromic
genes in male fertility. The fact that X- and Y-palindromes harbor testis-specific gene families makes them
ideal candidates for uncovering new genetic factors responsible for human spermatogenic defects. By
understanding the molecular functions of X- and Y-palindromic gene families, importa...

## Key facts

- **NIH application ID:** 9906246
- **Project number:** 5R01HD094736-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jacob L Mueller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,354
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906246

## Citation

> US National Institutes of Health, RePORTER application 9906246, Roles of X- and Y-palindromic Genes in Mammalian Fertility (5R01HD094736-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906246. Licensed CC0.

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