# The role Y chromosome genes Prssly and Teyorf1 in male reproduction.

> **NIH NIH R03** · UNIVERSITY OF HAWAII AT MANOA · 2021 · $72,542

## Abstract

Project Summary/Abstract
The mammalian Y chromosome is a symbol of maleness as it encodes the Sry gene driving male sex determination, a
battery of other genes thought to be involved in various aspects of male reproduction, and other genes playing roles of
broadly expressed regulators of transcription, translation and protein stability. In spite of these clearly important
functions, the knowledge linking the roles of specific Y chromosome genes to specific reproductive and other physiological
processes remains limited. This is due to the unusual genomic structure of this chromosome, which for decades rendered
it resistant to any targeting attempts. With the emergence of TALEN and CRISPR/Cas9 technologies addressing Y
chromosome gene function directly became possible.
The oddity of the Y chromosome structure made it also defiant to sequencing. The mouse Y chromosome sequence was
finally defined in 2014, 12 years after the remainder of the mouse genome was characterized. When the mouse Y sequence
was revealed two new single copy genes were identified on the Y short arm: Prssly (Y-linked serine-like protease) and
Teyorf1 (testis expressed, chromosome Y open reading frame 1). These genes were classified as ‘acquired genes’ and were
proposed to be the candidates for male fertility genes. Neither of these genes has been targeted and their function
remains unknown.
In Preliminary Data we show that Prssly and Teyorf1 expression is restricted to testicular postmeiotic germ cells. We also
analyzed PRSSLY and TEYORF1 predicted protein structure and function and found that both predicted proteins resemble
proteins that are known to play roles in spermatogenesis. PRSSLY belongs to the peptidase S1 family of proteins that
include serine proteases PRSS21 and PRSS55 essential for sperm motility and sperm ability to fertilize oocytes. TEYORF1
belongs to the Claudin family of proteins members of which were reported important for assembly and maintenance of
blood-testis barrier, a tissue barrier critical for normal spermatogenesis.
Acquisition to the Y chromosome, testis specific expression, and resemblance to proteins of known reproductive functions
prompted us to propose a hypothesis that Prssly and Teyorf1 play roles in male reproduction. We will address this
hypothesis pursuing two specific aims:
Aim 1: Generate Prssly and Teyorf1 knock-out (KO) and Prssly and Teyorf1 reporter tag knock-in (KI) mice using
CRISPR/Cas9 system and zygote electroporation.
Aim 2: Characterize phenotype of these mice focusing on assessment of fertility, sperm parameters, sperm function in
vitro, and spermatogenesis progression.
The combined results will allow to define whether Prssly and Teyorf1 play roles in spermatogenesis and fertility. The
development of KI mice will open the door to future mechanistic investigations of these factors. The project will impact
on understanding of Y chromosome gene function and genetic basis of male fertility. It will also contribute to discussions
...

## Key facts

- **NIH application ID:** 10337013
- **Project number:** 1R03HD106936-01
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Monika A Ward
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,542
- **Award type:** 1
- **Project period:** 2021-09-27 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337013

## Citation

> US National Institutes of Health, RePORTER application 10337013, The role Y chromosome genes Prssly and Teyorf1 in male reproduction. (1R03HD106936-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10337013. Licensed CC0.

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